Retina 2015 is kindly supported by Novartis

Retina 2015 is on Twitter at: #RetinaDublin @fightngblindness

Retina 2015 is kindly supported by an unrestricted educational grant from Novartis.

Thank you to the following companies who provided additional support to the Retina 2015 conference.

Delegates will be awarded 10 CPD points from the Irish College of Ophthalmologists.

Welcome to Delegates 4Retina 2015 Conference Speakers 6Story of the Retina Conference 8Scientific Programme 10Public Engagement Day Programme 12Retina Conference Roundtable Event 14The Fighting Blindness Story 16Fighting Blindness is Working for You 18European Year for Rare Disease 19Support Our Work and Our Members 20A Guide To Conditions of The Retina 22Support The National Vision Coalition 23Insight Counselling Service – Breaking the Isolation of Sight Loss 26Target 5000 – Gateway To Vision 28Medical and Scientific Advisory Board 30Jason Smyth – Fastest Paralympian on the Planet 32Áine Mae O’Mahony, Broadcaster and Fighting Blindness member 34Speaker Biographies and Abstracts 36The Geraldine Duggan Award 52Poster List 54Poster Abstracts 57Organising Committee 80Call for Expressions of Interest 82Join the Fight Agaist Blindness 83

Contents

Dear Delegate,

Welcome to Croke Park for the Retina Conference 2015. We are pleased that this event continues to be a useful platform to bring you, the innovators and health care providers together in the spirit of collaboration to discuss a collective vision for the future.

Fighting Blindness remains a patient-led charity with the aim of curing sight loss, supporting all of those affected and empowering patients and their families to be informed actors in the development of technologies, and implementation of policies that will improve their lives and those of future generations.

Since 1983 Fighting Blindness has funded and supported Irish research in the hope that we can CURE conditions that affect the retina, be they genetically inherited or age related. As research progresses from patient funded basic projects through to exciting discoveries, the development phase, to the advent of clinical trials and potential therapies, all stakeholders in our community have reached a critical time.

As patients we are buoyed by recent developments that demonstrate real potential to bring about positive change to those affected by sight loss through the delivery of novel therapies. While we await a new reality in therapeutic possibility, organisations like Fighting Blindness continue to work hard to provide the structures to SUPPORT patients on the journey from diagnosis with a retinal degeneration through to acceptance. The Insight Counselling Service at Ely Place, Dublin 2 is committed to creating a centre of excellence in the delivery of quality of life interventions for families, adults and children. Insight provides a suite of high level services from psychological support to a better understanding of technology, Through the arts and peer to peer group support and discussion, we have created a vibrant and dynamic community focused on breaking the isolation that sight loss can bring.

Welcome

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The 224,000 Irish people aff ected by sight loss and 285 million globally are encouraged by the great promise of innovation, brought about by you, can bring to us. We are aware that much work needs to be done to ensure that the clinical trial process is appropriate, particularly for small populations, and that the patient is listened to and respected as a critical voice at all stages in therapeutic development. Fighting Blindness is committed to supporting this voice through its education and outreach programme which includes events like today’s and tomorrow’s that EMPOWER you as the innovators to network, learn and forge new collaborations that will further expedite your scientifi c journey. Tomorrow we provide the opportunity for patients to learn from your experience and for you to learn from theirs.

As empowered patients, the members of Fighting Blindness stand with you and commit to do all that we can to support your work. We thank you for joining with us in dedicating your careers to bringing light and hope to millions of people worldwide who are facing a challenging diagnosis and an unexpected path. We thank you for working with us to develop a path to a brighter future.

I would like to thank the staff of Fighting Blindness for their dedication and commitment to the staging and facilitation of this and all of our events, our Board and organising committee, our MSAB and of course our speakers for traveling great distances to be with us today.

We will always be grateful to the founding members of Fighting Blindness who in 1983 had the vision and foresight to commit themselves to supporting research and for their dedication to a future we can all see.

Yours sincerely,

Avril DalyChief Executive, Fighting BlindnessAvril Daly

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1. Prof Eberhart Zrenner University of Tubingen and Tubingen Eye Hospital, Germany

2. Dr Shannon Boye University of Florida, USA

3. Dr Eric Pierce Massachusetts Eye and Ear Hospital and Harvard Medical School, USA

4. Dr Breandán Kennedy University College Dublin

5. Prof Rocio Herrero Vanrell University of Completense Madrid, Spain

6. Dr Volker Busskamp Center for Regenerative Therapies (CRTD) Dresden, Germany

7. Dr Joseph Carroll Medical College of Wisconsin, USA

8. Dr Deniz Dalkara Institut de la Vision in Paris, France

9. Dr Jasmina Cehajic-Kaptenaovic University of Manchester and Manchester Royal Eye Hospital, UK

10. Dr Stephen Rose Foundation Fighting Blindness, USA

11. Dr Graham Love Health Research Board

12. Christina Fasser President Retina International

13. Jason Smyth Fastest Paralympic Athlete on the Planet

14. Aine Mae O’Mahony Broadcaster and Fighting Blindness member

Thank you to all our speakers, session chairs and panellists for both the Scientific Programme and Public Engagement Day.

We appreciate your time and contribution.

Retina 2015 Speakers

The Retina Conference is an annual event organised by Irish patient-led charity Fighting Blindness, 2015 marks the 15th year of the conference. What began as the ‘All-Ireland Retinal Researchers Network (AIRRN)” Meeting in 2000 has grown from strength to strength over the years and is now a three day internationally renowned conference.

The aim of the conference is to bring together eminent fi gures in the global eff ort to fi nd treatments and cures for conditions causing sight loss. The event facilitates networking between Irish and international colleagues, leading to future collaborations and catalysing the next generation of vision research.

In 2011 the Retina conference was expanded to include a Public Engagement Day. People and families aff ected by sight loss, and members of the public were invited to attend and learn about developments in research and the importance of patient advocacy.

Now in its fi fth year, the Public Engagement Day off ers people a unique opportunity to engage with leading clinicians and researchers and provides a platform for Irish patients to learn about their condition and the research that is aiming to fi nd therapies to treat it.

In 2013 a third dimension was added to the conference, a clinical trials roundtable meeting. The purpose of this workshop is to discuss some of the roadblocks that face the development of clinical trials and that will infl uence the ultimate success rate of these trials, with a focus on diseases of the retina.

Retina Conference Story

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Wing Commander Professor Robert Scott from the Royal Centre for Defence Medicine, Birmingham pictured at Retina 2013

Prof John Flannery, University of California, Berkeley at Retina 2013

Minister for Health Leo Varadkar meeting speakers Prof Gustavo Aguirre, University of Pennsylvania and Dr Mark Pennesi, Casey Eye Institute, Oregan at Retina 2014

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Minister for Health Leo Varadkar discussing the Retina 2014 conference programme with Fighting Blindness CEO. Avril Daly and Consultant ophthalmic Surgeon. Mr David Keegan

Dr Maria Meehan and Anna Moran, Fighting Blindness pictured on the Croke Park Skyline with Dr Paul Kenna, Royal Victoria Eye and Ear Hospital and Trinity College Dublin, and former Dublin footballer Barney Rock

Prof Christian Grimm, University of Zurich and Prof Tom Cotter, University College Cork at Retina 2013

Delegates at the Retina 2014 conference, including Dr Breandán Kennedy and Dr Tahira Saad

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8.30am Registration and poster viewing

9.15am Opening Address Kevin Bowers, Chairperson of Fighting Blindness Prof Robin Ali, University College London, Chair of Fighting Blindness Medical and Scientific Advisory Board

9.40am Dr Graham Love: Health Research Board Public and Patient Involvement in Health Research

Session 1 Chair — Dr Maria Meehan, Fighting Blindness Research Manager

10.00am Prof Eberhart Zrenner: University of Tubingen and Tubingen Eye Hospital, Germany Treatment of hereditary retinal degeneration with transcorneal electric stimulation (TES)

10.30am Dr Shannon Boye: University of Florida, USA Gene Delivery to the Retina: Current and Emerging Technologies

11.00am Dr Stephen Rose, Foundation Fighting Blindness, USA The US Perspective

11.15am Jason Smyth, Fastest Paralympic Athlete on the Planet

11.30am Coffee Break and Poster Viewing

Session 2 Chair — Prof Alan Stitt, Queen’s University Belfast.

12.00pm Dr Volker Busskamp: CRTD Dresden, Germany Cell type-specific optogenetic vision restoration strategies

12.30pm Dr Breandán Kennedy: University College Dublin Pharmacological Restoration of Visual Function in a Blind Zebrafish Mutant Following Histone Deacetylase Inhibitor (HDACi) Treatment.

1.00pm Prof Rocio Herrero Vanrell: University of Completense Madrid, Spain Biodegradable Microparticulate Devices for the Treatment of Retinal Degenerative Diseases

1.30pm Aine Mae O’Mahony: Broadcaster and Fighting Blindness member

Retina 2015 Scientific Programme: Friday, November 6

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1:45pm Minister Aodhán Ó Ríordáin, TD - Formal Opening of Retina 2015

2.00pm Lunch

3.00pm Winning Poster Presentation Mr David Keegan, Fighting Blindness Board Member introduces The Geraldine Duggan Award, to be presented by Suzanne Duggan.

Session 3 Chair — Prof John Flannery, University of California, Berkeley

3.15pm Dr Deniz Dalkara: Institut de la Vision in Paris, France Optogenetics for vision restoration- translation from mice to non- human primates

3.45 pm Dr Jasmina Cehajic-Kaptenaovic: University of Manchester Restoration of Vision with Ectopic Expression of Human Rod Opsin

Session 4 Chair — Prof Brendan Buckley, ICON Plc and University College Cork

4:15pm Dr Joseph Carroll: Medical College of Wisconsin, USA High-Resolution Retinal Imaging and Clinical Trials - What’s Next?

4.45pm Dr Eric Pierce: Massachusetts Eye and Ear Hospital and Harvard Medical School, USA Studies of the Genetic Causality of Inherited Retinal Degeneration

5.15pm Christina Fasser, President Retina International

5.30pm Close

10.00am Coffee and registration

10.30am Welcome and Introduction Avril Daly, Fighting Blindness Chief Executive

10.45am Jason Smyth, Fastest Paralympian on the Planet

11.00am Session 1: Cure

Chair – Prof Tom Cotter, University College Cork

11.00am Dr Stephen Rose, Foundation Fighting Blindness, USA The US Perspective

11.15am Dr Shannon Boye – University Of Florida, USA Future Developments in Gene Therapy

11.45am Chair – Maria Meehan, Fighting Blindness Research Manager Panel Discussion: Why do therapies take so long to reach patients? Siobhan Gaynor, Genable Technologies Ltd Dr Paul Kenna, Royal Victoria Eye and Ear Hospital and Trinity College Dublin Prof John Flannery, University of California, Berkeley Christina Fasser, President of Retina International

12.30pm Breakout Sessions • Age-related macular degeneration (AMD) • Retinitis pigmentosa (RP) • Usher syndrome • Stargardt disease • Other inherited retinal degenerations

Retina 2015 Public Engagement Day: Saturday, November 7

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1.45pm Lunch

Chair - Caitriona Dunne, Fighting Blindness Communications & Advocacy Executive

2.45pm Session 2: Support

2.45pm Accessible Technology for Varying Levels of Vision Fighting Blindness members Cearbhall O’Meadhra and Conor Maguire

3.00pm John Delaney, Senior Counselling Manager, Insight Counselling Service Coping with the Challenges of Sight Loss

3.15pm Session 3: Empower

National Vision Coalition Manifesto Avril Daly, Fighting Blindness Chief Executive and Co-chair of the National Vision Coalition Mr David Keegan, Consultant Ophthalmic Surgeon and Fighting Blindness Board member Gerry Kerr, Fighting Blindness member and patient representative on National Vision Coalition

3.45pm Christina Fasser, President, Retina International

4.00pm Close

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Over the past number of years there has been remarkable progress made in the quest for treatments for retinal dystrophies, and many promising therapies are now at the translation phase from academic research to clinical stage research.

As part of the retina Conference, Fighting Blindness held a Roundtable event on Thursday, November 5. The event brings together all of the stakeholders involved in this clinical progression including ophthalmologists, optometrists, scientists, industry, the regulators and patients in order to discuss some of the roadblocks currently facing successful development of clinical trials for these myriad of conditions.

A major area for discussion is the identification of appropriate, objective clinical endpoints and standardisation of the measurement of these endpoints across trial sites. Importantly, the development of meaningful, patient-relevant endpoints and acceptance of these endpoints by the regulators is an area that Fighting Blindness is particularly focused on investigating.

We will be preparing a white paper of this discussion which will be available for circulation in the coming months. It is hoped that the outcome of this roundtable will stimulate discussions among researchers, funding agencies, industry and policy makers that will accelerate the development for safe and effective treatments for retinal dystrophies.

Retina ConferenceRoundtable Event

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Fighting Blindness started in 1983 as a group of families affected by rare, genetically inherited forms of sight loss coming together for support. The founders met regularly in Dublin’s Royal Victoria Eye and Ear Hospital to help each other cope with the reality of degenerating vision. At that time, genetic research into these conditions was maturing somewhat and the group, though small and without any form of scientific background, decided to investigate this new and exciting prospect.

In those pre-internet days, the only way to find out more information was through attending conferences and events, which were costly and not easy to get to. In 1984, a few members of the support group travelled to Helsinki, where the umbrella organisation Retina International held a scientific conference. The discussions on genetics piqued the Irish group’s interest, and within one year the group had raised £500,000 to establish its flagship project at Trinity College, Dublin (TCD) examining the genetic course of dominantly inherited retinitis pigmentosa (RP). In 1989, that very team in TCD discovered the first gene responsible for RP, and in 2011 that same project received a venture capital investment of €5 million to bring it towards the pre-clinical stage.

Since our founding, Fighting Blindness has invested over €15 million in more than 70 projects. We are proud to be an organisation enabling the progress of research that may not otherwise have been funded. We believe we are close to the goal we set 30 years ago, to find treatments and cures for blindness.

Fighting Blindness is an Irish, patient-led organisation with a vision to cure blindness, support people living with sight loss, and empower patients.

Cure We promote and facilitate the development of therapies which are accessible to all patients aff ected by sight loss. Our research strategy focuses on these fi ve pillars:• Genes and gene therapy• Cell technology and regenerative medicine• Retinal implant technology• Novel drug therapy• Population studies

SupportThe Insight Counselling Service provides support for people and families who are living with sight loss. It is not just the individual who may need support, but his/her partner, children, extended family and friends. We work with all those aff ected, directly and indirectly, by sight loss.

EmpowerFighting Blindness advocates on behalf of everyone in Ireland aff ected by severe vision impairment. We work in partnership with stakeholder groups in the areas of health, science, industry and government to ensure that the patient voice is represented in all matters. We advocate for equitable access to existing treatments, novel therapies and appropriate care.

Cure. Support. Empower

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In the development of health care provision in Ireland it is important to note that more than half of the legislation stems from EU policies and strategies. These include directives, regulations and recommendations. Fighting Blindness works closely with relevant EU bodies representing patients affected by both chronic and rare disease throughout Europe and continues to play a role in influencing EU policy makers on issues that concern our community.

We interact with the institutions governing the European Union, including the European Commission and European Parliament. We also work closely with EURORDIS – The European Organisation for Rare Diseases, EPF – The European Patient Forum and of course our umbrella organisation, Retina International. As the European Council represents national interests, advocacy efforts directed towards governments are most effective at the national level and can be performed in cooperation with all of these groups.We have played a role in advocating for the EU Regulations on Orphan Medicinal Products and Advanced Therapy Medicinal Products. The EU Commission communication Rare Diseases: Europe’s Challenges in 2008 led to the EU Council Recommendation on a European action in the field of rare diseases; this was instrumental in the development of national plans for rare diseases in all Member States. We have also worked with the aforementioned groups among others to ensure the transposition of emerging EU Directives, most recently that on Patients’ Right to Cross-Border Healthcare in 2011, now transposed in law.

A new legal instrument called European Reference Networks (ERNs) has recently been developed through the European Committee of Experts on Rare Diseases in order to facilitate the cross-border care of patients. These ERNs will comprise of 22 thematic groups that will be established to ensure that every patient with a rare disease finds a home. ERNs will also facilitate the development of care pathways and promotion of research and development of clinical trials for small populations.

One of the thematic groups will be for Rare Eye Disease and ERNs will become legally recognised instruments for EU funding in the future. This is critical for our community as research is embedded as core criteria for involvement in a network. Fighting Blindness and Retina International with the support of EURORDIS is currently working on identifying the Centres of Expertise (CEs) in each member state that wishes to be accredited under this new framework to become a Health Care Provider (HCP) or indeed Coordinator of the Network. This is a significant opportunity for the promotion of ophthalmic care in the EU and to highlight the value of such an entity in the provision of innovative care pathways for patients. For further information please contact Dr Maria Meehan at research@fightingblindness.ie

Fighting Blindnessis Working for You!

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European Year for Rare Diseases

Every year since 1983, the European Union has chosen a different topic for the European Year in order to raise awareness and encourage debate and dialogue within and between European countries. We want to make 2019 the European Year for Rare Diseases! This initiative presents a unique opportunity to build significant awareness both publically and politically for rare diseases and to foster more research in the field.

Why 2019?

2019 is an important year for the European rare disease movement. It marks the twenty-year anniversary of the adoption of the EU Regulation on Orphan Medicinal Products as well as the ten-year anniversary of the Council Recommendation on rare diseases. What better way to celebrate these major milestones than with a European Year for Rare Diseases!

A European Year for Rare Diseases would help find solutions both in the public and political spheres to the challenges that patients, families and care-givers face. It would encourage researchers to focus on rare diseases, and create conditions for better health, medical and social care for all. To register your support or for further information contact communications@fightingblindness.ie.

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HOW YOU CAN HELP

We’re a small charity with a big mission – funding sight saving research and supporting people living with sight loss in Ireland.

We can’t do this without you. 90% of our funds come through the kindness and generosity of the community and corporates.

Why not take on a Fighting Blindness Challenge to help raise much-needed funds?

Join us at the Hell & Back or Runamuck obstacle events – Terrific days out with a difference. There’s so many dates and distances to choose from.

For more information or for other fun events check out our Online Calendar at www.FightingBlindness.ie. And say hi – pop over to our Fundraising Hub Stall today!

“I could not have imagined how much fun it would all be and even before we embarked, I would not have thought I might want to do it again! I would highly recommend it to anyone interested in cycling, interested in taking on a challenge or interested in supporting Fighting Blindness.”

Tony Ward, Paris2Nice Cycle

Support our Work and our Members

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HOW YOUR COMPANY CAN HELP

Choose Fighting Blindness as your Charity of the Year. By supporting our work through a mutually beneficial partnership – everybody wins!

We will work with you to develop a tailored partnership plan best suited to you and your business.

Benefits to You and Your Team:

Impact: you’re actively helping the 224,000+ people in Ireland living with sight-loss.Increased Engagement & Morale: do good, feel good!Brand-Building: helping a small charity do big things enhances and builds your company brand.

For more on how your company can get involved pick up our Corporate Partnerships brochure at the Fundraising Hub or you can contact us at fundraising@fightingblindness.ie

Support our Work and our Members

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Fighting Blindness published ‘A Guide To Conditions Of The Retina’ in December 2014. Since that time the guide has been circulated, within Ireland and internationally, to patients, ophthalmologists, optometrists and other healthcare professionals.

The guide provides information about age-related macular degeneration (AMD) and diabetes-related sight loss, as well as a range of rare inherited retinal conditions including: retinitis pigmentosa, Stargardt disease, Usher syndrome, choroideremia, Leber congenital amaurosis (LCA), juvenile X-linked retinoschisis (XLRS), Leber hereditary optic neuropathy (LHON), Best disease, cone-rod dystrophies and achromatopsia.

The aim of this resource is to provide accessible, reliable and easily understandable information about conditions and research, and give details about support available for people and families living with sight loss.

The guide sets out information about the causes, symptoms, any available or potential therapies, and research into these conditions. It details how the eye works and defi nes the terms used to detail the parts of the eye, as well as highlighting the roles of the various eye health professionals that people come into contact with and what tests may be carried out at an appointment. A detailed overview of human genetics and explanation of inheritance patterns is also contained in the guide, as well as information about retinal research and the research process. Contact details and links for Irish and international patient, medical and research organisations are included for additional information and support.

The brochure was written by Fighting Blindness in collaboration with clinical and scientifi c experts who gave their guidance and input. It was designed primarily for people who have been diagnosed with a sight loss condition aff ecting the retina, and their families. It also serves as a reference tool for medical and healthcare professionals such as ophthalmologists, general practitioners and optometrists, among others.

A Guide To Conditions of the Retina is supported by Bayer Healthcare and proudly endorsed by the Irish College of Ophthalmologists (ICO), the Association of Optometrists in Ireland (AOI) and the Genetic and Rare Disorders Organisation (GRDO).

You can pick up a copy of A Guide To Conditions Of The Retina at the Fundraising Hub.

A Guide To Conditions of the Retina

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Deputy Mary Mitchell O’Connor T.D. speaking at the launch of A Guide To Conditions Of The Retina

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Investment in the development of treatments and cures for conditions causing sight loss need to be increased and policies that will ensure equitable and transparent access to the therapies that have and will emerge in the coming years need to be implemented. Fighting Blindness is central to this, working with all stakeholders in advocating for a National Framework for Vision Health in Ireland.

To learn more you can join us at The Alexander Hotel Dublin on the morning of Thursday, December 10 where we will launch our General Election Manifesto. This manifesto will call on the publication and implementation of a strategic approach to vision health that will provide adequate pathways for patients affected by sight loss by mapping their needs from diagnosis to medical intervention and rehabilitation.

The National Vision Coalition is a multi-stakeholder group created by Fighting Blindness and the National Council for the Blind in Ireland along with healthcare professionals, patient representatives and people working in vision-related advocacy and healthcare. The Coalition has been working together since 2012, calling for a strategic approach to vision health services in Ireland.

In 2013 the National Vision Coalition launched a comprehensive report recommending the implementation of a National Vision Strategy. The report - Framework to Adopt a Strategic Approach to Vision Health in Ireland - proposed eight principles* to guide the development of this strategy.

This framework document was followed in April 2014 with a report on the economic impact of eye disease in Ireland. The aim of the report – which is part of a pan-European study of 16 countries by Deloitte, was to analyse the impact and burden of blindness and the most prevalent eye diseases in Ireland, and to evaluate the cost-effectiveness of interventions to prevent eye disease and blindness. The National Vision Coalition further called on Government to develop a National Vision Strategy and highlighted the significant savings that could be made by its implementation. There are currently more than 220,000 people in Ireland who are blind or vision impaired, with this number expected to increase to almost 272,000 by 2020. Five people per week became blind in Ireland since 2010, despite 75 to 80% of blindness being preventable. The majority of these cases can be medically managed to prevent partial sight loss deteriorating to blindness.

Blindness and vision impairment cost the Irish state €205 million in 2010, yet up to €76 million could potentially be saved if a series of cost-effective measures for the four main eye diseases in Ireland – cataract, diabetic retinopathy, glaucoma and wet-age related macular degeneration (wet AMD) were implemented. This potential saving is particularly relevant since the cost of blindness is expected to increase to €2.5 billion by 2020.

Please Support The National Vision Coalition

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The Government committed to the World Health Organisation (WHO) objectives of Vision 2020 to eliminate avoidable blindness wherever possible by 2020.

With just four years left to meet this target, the Coalition’s eight principles have not yet been developed into a much-needed National Vision Strategy.

The Coalition acknowledges that attempts are being made by the Government to improve eye health services, such as the successful roll-out in February 2013 of Diabetic RetinaScreen – The National Diabetic Retinal Screening Programme. However, this programme is just one initiative required as part of a coordinated strategic approach at a national level.The key challenges, along with potential principles and key objectives for a national strategy, have been outlined to Government and put forward as recommendations. The challenges identified include insufficient resources, suboptimal levels of connectivity and integration and gaps in the continuum of care. The coalition emphasise the need to balance commitments between prevention, cure and care while addressing the deficits in knowledge, information and research in the area.

A statement calling on the development of a National Vision Strategy has been raised in the Dáil by Deputy Mary Mitchell O’Connor, TD. A motion raised in the Seanad by Senator Martin Conway received cross-party support and was backed unanimously by the Seanad last year. However, at this time we still await a commitment from Government towards the development of a National Vision Strategy.

*Eight guiding principles to direct future development of vision health services and support in Ireland:

1. Any future strategy should be all-encompassing and include all eye health problems and diseases for both children and adults

2. Quality and safety need to be maximised for anyone accessing services

3. Services should be person-centred4. Patients should have choice and

control and the ability to live fulfilled lives

5. Seamless service pathways should be put in place

6. Evidence-based approaches and equality of access should be prioritised

7. Research should also be prioritised8. The strategic development of eye

health should be aligned with the wider public health policy framework.

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Members of the National Vision Coalition pictured outside the Dáil in July 2014.

National Vision Coalition members: Lynda McGivney-Nolan, Association Of Optometrists Ireland; Des Kenny, NCBI; Siobhan Kelly, Irish College of Ophthalmologists; Avril Daly, Fighting Blindness; Padraig Mallon, Irish Guide Dogs.

Fighting Blindness started in 1983 as a group of patients coming together to support each other. Over the last 32 years, support has remained central to our work. The diagnosis of a condition causing sight loss can be devastating, not only to families with a history of the condition but also to those who had no idea and are now faced with the loss of their sight.

In 2002, Fighting Blindness established the Insight Counselling Centre to provide professional psychotherapy services for people and families living with sight loss. Since then Insight has expanded its range of services and its geographical reach around the country. It is now a national service taking a whole person quality of life approach to new programmes that complement its traditional counselling services, monthly peer support groups and weekly technology group meeting.

The issue of mobility is a crucial one for anyone dealing with sight loss. Getting to work, school or to the shops can often become a logistical challenge and sometimes an emotionally distressing one as well. This is not helped by the fact that public transport systems outside major areas of population tend to be limited in terms of routes and frequencies. In recognition of such difficulties we launched our nationwide telephone counselling service in September 2014 to enable people access our service with ease, irrespective of where they live. This has proved to be a vital connection for people living all over Ireland.

A new initiative called the Visionaries Music School was launched in June 2015. Based on the Greenberg Music School at the Lighthouse Guild, New York, the Visionaries Music School promotes the role of music to enhance the lives of people with a visual impairment. The first 12 week term of the music school was a great success and a second term is now underway along with a recently formed VIP Choir.

Sight is probably our most treasured sense, and the thought of losing it naturally gives rise to feelings of fear and uncertainty about the future. The issues that a person with sight loss faces are both practical and psychological in nature as one makes the transition from a sighted to a partially or even non-sighted lifestyle. The journey of adapting and coping with new and uninvited circumstance is unique for each individual.

Insight Counselling ServiceBreaking the Isolation of sight Loss

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John Delany, Senior Counselling Manager, Insight Counselling Service

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That needs to be understood and respected by all who off er encouragement and assistance in order to ensure that the process of adjustment is not impeded.

Providing emotional support to people and families living with sight loss is essential. It is not just the individual with sight loss who is aff ected but also their partner, children, extended family and friends. At Insight, we work with all those aff ected directly and indirectly by sight loss.

For more information about the Insight Counselling Service please contact John Delany, Senior Counselling Manager on 01 674 6496 or insight@fi ghtingblindness.ie.

“Sight loss is a life changing experience, but not a life ending one.”

Frank Kelly, Choir Master of Visionaries Choir

Albert Brown and Paul Griffi th at the Insight technology peer support group — The Exchange Club

Target 5000 is a Fighting Blindness research project which aims to provide a genetic diagnosis for the estimated 5,000 people on the island of Ireland who have a genetic retinal condition.

Target 5000 is the most ambitious project that Fighting Blindness has undertaken to date. The purpose of the project is to identify every retinal disease causing gene mutation in the Irish population by DNA sequencing the estimated 5,000 Irish people believed to have a degenerative retinal condition. Target 5000 represents a vital and progressive step in facilitating the movement of laboratory research towards treatment.

The project began in 2012 as Target 3000 and was based solely in the Republic of Ireland, with two sites in Dublin. In 2014 it was expanded to include a site in Belfast and became an all-Ireland project. The project is led by three ophthalmologists. Dr Paul Kenna in the Royal Victoria Eye and Ear Hospital, Dublin; Mr David Keegan in the Mater Misericordiae University Hospital, Dublin and Ms Giuliana Silvestri in the Royal Victoria Hospital, Belfast.

Until now, one of the challenges confronted by someone who has one of these conditions was the lack of a precise diagnosis. Because it is often difficult to tell which specific type of retinal disease a patient has based on just looking at the eye, there have been several cases where a patient has been given a clinical diagnosis of one condition but found to have a different condition after genetic testing. Inherited retinal diseases are some of the most complicated of all genetic conditions, involving more than 200 genes. Receiving a complete diagnosis requires genetic testing. Through genetic screening of the person affected and their family members, Target 5000 will provide more detailed information about the nature and inheritance pattern of the condition – this is vital information for patients.

The researchers firstly investigate known mutations in known genes associated with retinal degenerations. There are approximately 200 genes known so far, and these are estimated to account for conditions in about 60% of people affected. If the gene is not found in this initial testing then further work is needed to investigate the entire exome.

Target 5000 Gateway to Vision

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The information obtained from the Target 5000 project will be added to a National Patient Registry. This registry will enable patients who are eligible for clinical trials to be identified in the future.

In 2014 after recognising the large volume of work needed for such an ambitious project, Fighting Blindness began supporting two clinical fellows to work on Target 5000 in the Royal Victoria Eye and Ear Hospital and the Mater Misericordiae University Hospital. This extra resource immediately bolstered the activity on this important study, and we are grateful for their enormous help.

Through the tireless efforts of these clinicians, almost 900 individuals have already registered to take part in the project and have donated a blood sample. We thank each and every patient for giving their time to participate in this important study and we look forward to further engaging with them to build our registry into the future.

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“I am very pleased to be involved with Fighting Blindness as I believe that international collaboration between scientists and clinicians is vital for accelerating the development of new treatments. I have served as Chief Scientific Advisor and Chair of the MSAB for over 6 years.”

Prof Robin Ali

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Fighting Blindness has a strong and dynamic Medical and Scientific Advisory Board. The MSAB plays a valuable role in advising the Board of Directors and its Research Sub-Committee, with regard to the research strategy. The group assists in appraising new grant applications, and identifying international peer reviewers. It also monitors on-going programmes and where appropriate, offers recommendations regarding research policies and strategic plans, helping the executive to ensure that the excellent quality of our research is maintained.

The MSAB includes Irish and international representatives, all of whom are experts in medical research, including but not limited to retinal research. The group is chaired by Prof Robin Ali who serves as the Chief Scientific Officer for Fighting Blindness.

1. Prof Robin AliProfessor of Human Molecular Genetics, Institute of Ophthalmology, University College London

2. Prof Frank BarryProfessor of Cellular Therapy, Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway

3. Prof Brendan BuckleyChief Medical Officer, ICON Plc. And Clinical Professor, Pharmacology and Medicine, University College Cork

4. Prof Alan StittDirector, Centre for Vision and Vascular Research, Queen’s University Belfast, Northern Ireland

5. Prof Alberto AuricchioProfessor of Medical Genetics, Frederico II University / TIGEM, Naples, Italy

6. Prof John FlanneryProfessor of Neurobiology, University of California, Berkeley, USA

7. Dr Joseph CarrollCo-director of Advanced Ocular Imaging Program (AOIP),Medical College of Wisconsin, USA

Medical and ScientificAdvisory Board

Jason Smyth, from Derry, was diagnosed with Stargardt disease at age 8. The condition, which affects his central vision, has deteriorated since then and he now has approximately 10% vision. While this affected his social life as a teenager, it never slowed him down and he always excelled in sport.

When he was sixteen he was approached by his PE teacher about joining an athletics club. His talent was quickly noticed and before long he was winning national titles in schools competitions, including the Irish Schools Championships three years in a row. By this time he had also become involved with Paralympics sport and had competed in, won, and set new world records in the 100m and 200m T13 races at the European and World Paralympic Championships.

In 2008 Jason competed at the Beijing Paralympic Games where he took gold in the T13 100m and 200m, breaking the world record in both. In 2010 he became the first Paralympic athlete to qualify and complete in the able-bodied European Championships, making it to the semi-final in the 100m. He then went on to qualify and race in the able-bodied World Championships in 2011.

From 2008 to 2012 Jason trained in Florida, working towards gaining the qualifying time for the Olympics 100m. He achieved the Olympic B standard in 2011 when he ran a personal best of 10.22 seconds, but fell 0.04 seconds short of the A standard and missed out on competing in the 2012 London Olympics. Jason again won two gold medals at the London 2012 Paralympic Games in the 100m and 200m races, breaking two world records in the process and earning himself the title of ‘Fastest Paralympian on the Planet’.

Jason again won gold in both the 100m and 200m in the European Paralympic Championships in August 2014.

On September 7 last Jason competed in a ‘Champion of Champions’ 100m race in Rio de Janeiro. The event was organised by the Rio 2016 Paralympic Committee to mark one year to go until the opening ceremony of Rio 2016. The top sprinters from each Paralympic category went head to head for the first time ever to determine the official “Fastest Paralympin on the Planet”. Jason reaffirmed his title with a convincing win, crossing the line in 10.63 seconds.

Jason is currently living and training in the UK for the Rio 2015 Paralympic Games.

Jason SmythFastest Paralympian on the Planet

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Áine Mae O’Mahony manages a community radio station in Loop Head, Co Clare. Prior to this she owned a café in Ennistymon, Co Clare and studied Visual Media in Cork.Áine Mae has been a Fighting Blindness member since 2008. She has contributed immensely to the organisation as a patient advocate, spokesperson and through various fundraising activities.

In July 2013, as part of the National Vision Coalition launch of a Framework to Adopt a Strategic Approach to Vision Health in Ireland, Áine Mae spoke to TDs about her own experience of eye health care in Ireland following her sudden onset blindness caused by glaucoma and detached retina in 2006. She spoke from the patient perspective on the importance of joined-up thinking in the health care system, the power of collaboration between all stakeholders and the education needed to increase the understanding that sight loss has many degrees and can sometimes be a “hidden disability”, not immediately obvious to the onlooker. Áine Mae’s contribution was eloquent and realistic and highlighted the focus of Fighting Blindness to empower patients, ensuring that the patient voice is always included in any discussion regarding patient care and policy development.

Áine Mae is a fantastic ambassador for Fighting Blindness and the entire vision community and we are delighted to welcome her to Retina 2015 to represent the voice of the Fighting Blindness membership.

“No pun intended, but I have always looked on the bright side of life, and the first thing to say is that, if you have to go blind, there has never been a better time than now. Even 20 years ago, losing my sight would have meant losing my independence. Job opportunities would have been limited to say the least. But today there is nothing that a sighted person can do on a computer that I can’t do just as well, if not better. I am a great believer in the benefits of a positive mental attitude. I don’t dwell on what I can’t do. I focus on what I can do, and – bar the obvious like driving – you can do practically anything if you do it in a certain way.”

Áine Mae O’MahonyBroadcaster and Fighting Blindness member

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Speaker Biographiesand Abstracts

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Dr Graham Love, Health Research Board

Dr Graham Love is Chief Executive of the Health Research Board (HRB), an agency of the Irish Government’s Department of Health. The HRB manages a €100 million investment portfolio spanning clinical, population and health services research. It also manages key health information systems and provides evidence-based policy support to the Irish Government’s Department of Health.

Previously Graham worked in Science Foundation Ireland, covering a variety of areas including strategy, communications and programmes, where he filled senior roles such as Head of Strategy, Director of Policy and Interim Director General. Before entering the Public Service, Graham was in the private sector for many years working for management consulting firm Accenture. There he worked with international clients such as Microsoft, Vodafone and Norsk Hydro on a range of projects including IT system implementations, strategic reviews and transformational change. He lives with his family in Dublin.

Prof Eberhart Zrenner, University of Tubingen and Tubingen Eye Hospital, Germany

Dr. Zrenner is Senior Professor of Ophthalmology at the Institute for Ophthalmic Research at the Centre for Ophthalmology of the University of Tuebingen, Germany. His research interests include: retinal physiology and pathophysiology, neuro-ophthalmology, ophthalmic toxicology, retina implants, electrophysiology and other methods of non-invasive function testing, neurodegeneration and ophthalmogenetics. He coordinates 3 EU-Projects. He also is Principal Investigator of several clinical studies and has developed a subretinal active microphotodiode array (MPDAs) to replace degenerated photoreceptors, so far tested in 29 study patients in an international multicenter trial, including Oxford, London and Hongkong and others, now approved for commercial use as medical device (CE-mark).

He has studied electronic engineering as well as medicine at the Technical University Munich, where he obtained his MD degree in 1972. Subsequently worked within the Max-Planck-Society with Eberhard Dodt for 16 years and received a Fogarty fellowship at the national Eye Institute, NIH, Bethesda, MD (1977 and 1978), studying temporal, spatial and chromatic characteristics of retinal ganglion cells via extracellular recordings in monkey retina with Peter Gouras. After acquiring a PhD degree he received an associated professorship at the University Eye Hospital in Munich. He became full professor University Eye Hospital in Tuebingen

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in 1989, now Center for Ophthalmology. There he founded the Institute for Ophthalmic Research and runs a special clinic for hereditary retinal degenerations. He has received numerous grants and awards, two honorary Doctoral Degrees and has published approximately 490 peer reviewed papers.

Treatment of hereditary retinal degeneration with transcorneal electric stimulation (TES)

Eberhart Zrenner1, Florian Gekeler1,2, Mariya Gosheva1, Andreas Schatz1,

1) Centre for Ophthalmology, University of Tuebingen, Germany; 2) Klinikum Stuttgart, Germany

Results in several animal experiments have supported the beneficial effects of transcorneal electrical stimulation (TES) on the retinas of rats in vivo and in vitro on the survival of various retinal cell populations. Neuroprotective effects due to release of endogenous growth factors by TES have been observed in several preclinical studies (see review of Fu et al., Graefes Archive 253: 171, 2015).

In order to assess the safety of TES and explore its efficacy, 24 patients with retinitis pigmentosa (RP) underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks in a prospective, randomized, partially blinded, good-clinical-practice study (Schatz et al IOVS 2011). No serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and dark adapted b-wave amplitude reached statistical significance for improvement (P < 0.027 and P <0.001, respectively). Meanwhile, a commercial device OkuStim® (by Okuvision GmbH, Germany) is available in post-marketing surveillance studies for RP patients in several countries.

A further prospective sham-controlled follow-up TES- study was performed over 1 year in 63 RP patients to assess efficacy of treatment with this device. Patients were randomly assigned to sham, 150%, or 200% stimulation current of their individual electrical phosphene threshold. Primary outcome measure was visual field area (VFA; Goldmann III/4e), secondary outcome measures ganzfeld and mfERG values, BCVA, threshold to full field stimuli (FST; Diagnosys), assessed in week 1, 10, 16, 22, 28, 40, 46, 52.

Fifty-two patients (27 m, 25 w; TES=sham: n=20, TES=150%:

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n=15 and TES=200%: n=17) completed the study. As described by Gekeler et al (ARVO 2015) adverse events (AEs) were mainly dry eye symptoms. No serious AEs related to the treatment were observed. VFA decreased less in the 200% group, showing a tendency but not reaching significance (REML, p=0.19), as in the initial study. However, cone b-waves showed a highly significant increase in amplitude and shortening of implicit in the 200% group.

Summary: TES was found to be safe, AEs were mainly dry eye feelings always treatable by artificial tears. Primary and secondary outcome measure showed positive tendencies. Cone related functions did reach levels of statistical significance, as seen in the VF in the first study by Schatz et al. 2011. In a larger recent study significant improvements were also found in the cone ERG. Exploratory analyses on high responders were promising to identify patients who might benefit from TES.

Dr Shannon Boye, University Of Florida, USA

Dr. Shannon E. Boye received her B.S. in Marine Biology/Chemistry from Fairleigh Dickinson University in 2001 and a Ph.D. in Neuroscience from the University of Florida in 2006. Following a postdoctoral fellowship under Dr. William Hauswirth, she was appointed as Assistant Professor of Ophthalmology at the University of Florida (2012). Dr. Boye’s lab currently focuses heavily on four areas of research. (1) Developing a gene therapy for GUCY2D Leber congenital amaurosis (LCA1)- her team has demonstrated the ability to restore visually-guided behavior and preserve retinal structure in several animal models of LCA1 and they are now working with Genzyme/Sanofi to bring this treatment to the clinic. (2) Optimizing AAV vectors to target genes to photoreceptors following intravitreal injection- there is a need to develop an injection procedure which is less invasive than the state of the art (subretinal injection), particularly when an underlying genetic defect leads to a degenerative process and a fragile retina prone to further damage upon surgically induced retinal detachment. Dr. Boye seeks to develop AAV vectors that possess an enhanced ability to transduce photoreceptor cells, notably foveal cones, following intravitreal delivery. (3) Expanding AAV vector technology- Dr. Boye is actively developing novel, dual AAV vector platforms which are capable of delivering large transgenes. Once thought to be a limiting factor for AAV gene delivery, this technology will allow for the treatment of many diseases associated with mutations in large genes (>~5kb). Specific emphasis is placed on MyosinVIIa Usher syndrome (USH1b) (4) Developing gene therapies for diseases associated

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with defects in retinal bipolar cells. Using novel serotypes identified in her other research aims, her lab is investigating the ability to specifically target therapeutic genes to ON bipolar cells and restore retinal function to models of bipolar-mediated disease such as Congenital Stationary Night Blindness (CSNB).

Gene Delivery to the Retina: Current and Emerging Technologies

Dr. Boye will summarize efforts to develop gene therapies for photoreceptor-mediated, inherited retinal disease (something not yet addressed in the clinic). She will begin by describing her team’s efforts to develop a gene replacement therapy for GUCY2D Leber congenital amaurosis (LCA1), highlighting proof-of-concept studies in various animal models, Adeno associated virus (AAV) transduction studies in non-human primate and how these results relate to findings in the LCA1 patient population. While LCA1 is considered to be a great target for treatment via subretinal vector injection, there are many other inherited retinal diseases accompanied by relatively more retinal degeneration that would benefit from a less invasive injection procedure. Dr. Boye will briefly summarize efforts to develop AAV vectors that possess an enhanced ability to transduce photoreceptor cells following intravitreal delivery.

Dr Stephen M. Rose, Chief Research Officer, Foundation Fighting Blindness, USA

Dr. Rose joined the Foundation Fighting Blindness as the Chief Research Officer in December 2004. He manages and oversees the day-to-day operations of the Science Department, works closely with the Foundation’s Scientific Advisory Board and Science Liaison Committee, and provides overall leadership to its funding program. In addition, Dr. Rose and the Chief Drug Development Officer of the Foundation Fighting Blindness Clinical Research Institute (FFB CRI), the clinical arm of the Foundation work in concert to establish a seamless pipeline of science and clinical studies to move preventions and treatments into clinical trials while partnering with pharma and biotech to maximize potential commercialization.

Prior to joining the Foundation, Dr. Rose served Director, Division of Clinical Recombinant DNA Research, Office of Biotechnology Activities (OBA), NIH Office of Science Policy. In this position, he served as the Executive Secretary for the Recombinant DNA Advisory Committee and provided oversight and coordination for the recombinant DNA program to address issues regarding

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recombinant DNA, including human gene transfer clinical protocols.

Before joining OBA, Dr. Rose was Director of the Office of Clinical Applications in the Division of Allergy, Immunology and Transplantation at the National Institute of Allergy and Infectious Diseases. Before accepting that position, Dr. Rose was the Chief of the Transplantation Immunobiology Branch in the same NIAID Division and established the kidney transplant clinical trial program.

Dr. Rose received his B.S. in Biology with Honors from American University and his Ph.D. from the University of Virginia. Upon completion of his doctorate, he was a NIH postdoctoral fellow at Washington University in St. Louis. He also held academic positions at the University of Texas Southwestern Medical School and the University of New Mexico Cancer Research Center. Dr. Rose currently sits on the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee and is a Health Research Alliance Board member.

Dr. Volker Busskamp, Center for Regenerative Therapies (CRTD), Dresden, Germany

Dr. Volker Busskamp is a research group leader and a “Freigeist” fellow at the Center for Regenerative Therapies of the Technical University Dresden (CRTD), Germany. His research aims to drive human induced pluripotent stem (iPS) cells to neurons for disease modeling with a focus on entire neuronal circuit assembly to obtain sophisticated human test beds. His group specifically develops and applies protocols to generate retinal cell types of therapeutic interest from human iPS cells that will also be subjected to cell replacement therapies.

Volker Busskamp graduated in Biotechnology at the Technical University Braunschweig in Germany in 2006 and performed his postgraduate studies in Biology in Geneva, Switzerland in 2007. In 2010, he finished his PhD work in the laboratory of Botond Roska at the Friedrich Miescher Institute of Biomedical Research in Basel, Switzerland, on optogenetic repair of mouse and human photoreceptors. In addition, he studied the function of non-coding miRNAs in photoreceptors in health and disease. In 2011, Volker Busskamp joined George Church’s laboratory at the Harvard Medical School in Boston, USA for his postdoctoral training. He focused on revealing the biological rules of human iPS neurogenesis applying systems biology. In 2014, he started his independent research position at the CRTD funded by the Volkswagen Foundation “Freigeist” program.

©CRTD

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Cell type-specific optogenetic vision restoration strategies.

In retinal degenerative diseases such as Retinitis pigmentosa (RP) rod photoreceptors, important for night vision, degenerate whereas cones, important for high acuity daytime and color vision, lose their light-sensitive outer segments and become non functional. RP patients progressively lose their vision. I will present that single opto-gene therapeutic interventions to strategically important cell types in blind RP retinas restores light sensitivity.

We delivered Channelrhodopsin-2 or microbial halorhodopsins to RP retinas and restricted the expression to distinct retinal neurons by cell-type-specific promoter elements. Both opto-genes conferred light-sensitivity to former blind retinas. Resensitized retinas were analyzed by molecular biological, imaging and electrophysiological techniques. Furthermore, one approach was successfully translated to post-mortem ex vivo human retinas demonstrating its clinical prospects. Currently, the clinical trials for these cell type-specific therapeutic interventions have started (http://www.gensight-biologics.com).

Another attempt was to regenerate the light-sensitive antennas, the outer segments, of photoreceptors to restore the activity of the intrinsic phototransduction cascade. To this end, we identified a non-coding miRNA cluster being involved in the maintenance and function of this subcellular compartment in vivo. By applying these miRNAs specifically to stem cell-derived photoreceptors in 3d retinal organoids, we successfully generated light-sensitive outer segments.

Our results demonstrate that, despite the diverse genetic origin of RP, the targeted expression of opto-genes to retinal neurons can restore significant functionality to the visual system following degenerative changes. Furthermore, non-coding miRNAs might help to repair persisting photoreceptor cells.

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Dr Breandán Kennedy, University College Dublin

Dr. Breandán Kennedy is a Fighting Blindness funded researcher and head of the 3D-NET Industry – Academia consortium. He is also a senior lecturer and Head of Pharmacology in University College Dublin. He is a Research Fellow of the Conway Institute at UCD.

The main objective of Breandán’s research group is to develop genetic and pharmacological treatments for human blindness. Using zebrafi sh as an in vivo system, they have identifi ed several families with inherited blindness and have used these to characterise disease progression and evaluate therapies. They have also developed in vivo assays enabling us to discover novel drugs with specifi c neuroprotectant, anti-angiogenic or toxic propertiers in the eye.

Technology platforms include: zebrafi sh: development, expression profi ling, genetics,transgenics, morphants and drug screens; Retina: Morphology and Function.

Dr. Kennedy’s group focuses on three primary areas of research.

(1) Molecular Genetics of Vision and Blindness. The objective here is to better understand the factors that regulate normal development and function of vision, as well as, genetic mutations linked to blindness. The group’s approaches include generation of zebrafi sh models of inherited blindness or transcriptome and proteomic profi ling of eye development and cone photoreceptors.

(2) Ocular Drug Discovery. Breandán’s research group seeks to discover and develop drugs that modulate pathologies associated with blindness (e.g. angiogenesis, vessel permeability, infl ammation & neurodegeneration). They apply random or targeted drug screening methods in zebrafi sh (GFP reporter lines or behavioural assays) and progress hits to assays in human cell lines, explant tissue and pre-clinical rodent models.

(3) Ocular Drug Delivery. To enable sustained drug release in the posterior eye they are developing drugs encapsulated into microparticles. In collaboration with RCSI and NUIG, they have manufactured PLGA and HA drug loaded microparticles and are testing the pharmacokinetics of drug release and the safety and effi cacy of the microparticles.

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Pharmacological Restoration of Visual Function in a Blind Zebrafish Mutant Following Histone Deacetylase Inhibitor (HDACi) Treatment.

Background: Controversially, pharmacological inhibition of Histone Deacetylase (HDAC) proteins is in clinical trial for the treatment of inherited retinal degenerations. Previous studies report that patients suffering from the inherited retinal degeneration Retinitis Pigmentosa (RP) may show improved visual field and acuity following treatment with the HDAC inhibitor valproic acid (VPA). Utilising zebrafish models of retinal degeneration we rescued retinal morphology and visual function of a blind zebrafish mutant (dye mutant) by treatment with HDACi.

Methods: Visual function was assessed by Optokinetic Response (OKR) and Visual Motor Response (VMR) assays. Cone photoreceptor outer segment (OS) morphology, ciliary marginal zone (CMZ) apoptosis and cone photoreceptor outer segment (OS) length were assessed by light microscopy. Larvae were drug treated with HDACi (1 µM TSA, 10 µM MC1568 and 10 µM MS275) with or without 100-500 nM ANA-12 from 3-5 dpf at 28.5 °C. An unbiased shotgun proteomic analysis of TSA-treated dye eyes was carried out by LC-MS/MS and the resulting dataset analysed by Ingenuity Pathway Analysis (IPA) software.

Results: The dye mutant has reduced visual behaviour and several defects in retinal morphology compared to sibling larvae. HDACi treatment of dye results in improved OKR and VMR, rescue of gross morphological defects, an 80% decrease in the number of dead cells in the CMZ and an increase in cone photoreceptor OS length. Proteomic analysis identified significantly differentially expressed proteins in response to treatment, and pathway analysis identified BDNF as a major contributing mechanism to rescue. ANA-12 treatment blocks BDNF/Trkb signaling and HDACi mediated rescue in dye.

Conclusions: HDAC inhibition is effective in restoring visual function and rescuing morphological defects in a zebrafish model of retinal degeneration.

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Prof Rocio Herrero Vanrell, University of Completense Madrid, Spain

Rocío Herrero-Vanrell received her Ph.D. in Pharmaceutical Technology at the Complutense University of Madrid (UCM), Spain, in 1991. Currently, she is Professor of Pharmaceutical Technology and Biopharmaceutics at the Faculty of Pharmacy (UCM). Dr. Herrero-Vanrell has worked as a postdoctoral fellow at the Schepens Eye Research Institute, Massachusetts Eye and Ear (Harvard Medical School, Boston, MA, EEUU) from 1992 to 1993. Currently, she is head of a multidisciplinary research group (UCM 920415) dedicated to the development and evaluation of novel ophthalmic formulations. Pharmacists, ophthalmologists and veterinary surgeons constitute the research team. Her main research fields are ocular drug delivery with special expertise in microencapsulation of drugs for the treatment of posterior segment diseases, innovation of ophthalmic formulations and development of novel formulations for the treatment of dry eye and glaucoma. She has published more than 50 scientific articles related to the ocular field in internationally journals and serves on the editorial board of the scientific ophthalmic journal “Archives of the Spanish Ophthalmology Society” since 2000. She has served as a member of the Coordination Team of the Materials Science and Technology of the Spanish Agency of Research (ANEP) in the area of Biomaterials and Polymers. Her research funding has been from the Spanish Ministry of Economy and Competitiveness, Health Ministry, European Union and collaborations with Pharmaceutical Industry.

Biodegradable Microparticulate Devices For The Treatment of Retinal Degenerative Diseases

Retinal degenerative diseases are becoming more prevalent due to the increase in society longevity. Most of these pathologies are chronic and multifactorial. Due to their chronicity, successful therapy requires effective concentrations of the active substance in the target site for extended periods of time. Furthermore, administration close to the site of action is usually needed and intraocular injections are frequently employed. However, successive intravitreal injections are associated with non-desired effects and the risk of adverse events increases with the number of injections. Intravitreal administration of biodegradable microspheres (MSs) offers an excellent alternative to multiple administrations, as they are able to deliver the active substance in a controlled fashion for extended periods of time and disappear from the site of injection after delivering the drug. Furthermore, contrary to larger devices, administration of MSs is performed without the need of surgical procedures. Among the biodegradable

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polymers, poly (lactic) (PLA) and poly (lactic-co-glycolic) (PLGA) derivatives are the most employed. Under the technological point of view, the properties of the microspheres can be improved by the use of additives. Additionally, MSs can include more than one therapeutic molecule resulting especially useful for the treatment of multifactorial intraocular diseases. Personalized therapy can be easily achieved by selecting the amount of microspheres depending on patient’s needs. Support: MICINN MAT 2013–43127R; UCM-Research-Group 920415, OFTARED RD12/0034/0003.

Dr Deniz DalkaraInstitut de la Vision in Paris, France

Deniz Dalkara is a tenured researcher in INSERM, France and leads an emerging team on gene therapies and animal models of neurodegenerative disease at the Vision Institute in Paris. She graduated from Middle East technical University with a B.S. degree in Biology in 2001. Afterwards, she obtained a masters degree in pharmacology and pharmacochemistry in Strasbourg, France where she later pursued a PhD degree in cellular and molecular aspects of biology. She was awarded the Biovalley PhD thesis for method of protein delivery developed during her graduate studies, which was subsequently commercialized under the name “Pulse In” by Polyplus transfections. Later on she conducted a postdoctoral fellowship in the laboratory of Ernst Babmerg at the Max Planck Institute of Biophysics before moving on to UC Berkeley to do a second post-doctoral training in 2007. At UC Berkeley, Dr Dalkara applied viral engineering principals to enhance AAV vectors for their application in retinal degenerative diseases. Her work includes molecular evolution and engineering of viral gene delivery vehicles and their application to develop innovative gene therapeutic strategies to combat blinding diseases of the retina in mouse models of disease. In 2012 Dr Dalkara received the Young Investigator award to start her group at the Vision Institute in Paris and has been carrying on her research activities in this research institute with a strong focus on translational research.

Optogenetics For Vision Restoration — Translation From Mice To Non-Human Primates

Optogenetics is a biological technique, which uses light to control neurons genetically modified to express light-sensitive membrane proteins. It has become a widely used strategy in research with therapeutic applications ranging from cardiology to neurology. In terms of its clinical application, vision restoration in blind patients

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is likely to come first due to the existence of an optical window to the retina and thanks to established success of gene therapy in the ocular compartment. Microbial type opsins as well as vertebrate opsins have shown promise in restoring visual responses in blind rodents and other small animals. However, it was not clear if such treatments can be translated to humans. The major challenges in translating optogenetics from mice to man are related to the lack of optimized viral vectors for targeting various populations of neurons in the primate retina and to the dose extrapolation, going from small animal eyes with minimal immune responses to a large primate eye with immune surveillance. High-level opsin expression is necessary to generate light responses in blind retinas and achieving such expression levels in a large primate eye may come at the expense of a prohibitive viral dose triggering immune responses to both the vector and the transgene. In order to deal with these translational challenges, we studied combinations of adeno-associated virus (AAV) vectors and promoters to target optogenetic proteins to different subsets of neurons in the non-human primate retina. Our data show that successful expression of optogenetic proteins in the primate retina is cell type dependent. Furthermore, we highlight safety and efficacy of optogenetics for cell types that can be efficiently targeted with vector promoter combinations optimized for primates. Challenges remain for targeting certain neuronal populations with existing AAV technologies and for testing functional outcomes in vivo.

Dr Jasmina Cehajic-Kaptenaovic, University of Manchester and Manchester Royal Eye Hospital, Uk

Dr Jasmina Cehajic-Kaptenaovic, University of Manchester, UKDr Cehajic-Kaptenaovic is a clinician scientist at the Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester and Manchester Royal Eye Hospital and Manchester Academic Health Sciences Centre. Jasmina graduated from University of Oxford with Masters in Physiological Sciences and honours in BMBCh. She has undertaken specialist training in ophthalmology at St Thomas’ and Kings Hospitals in London and at Manchester Royal Eye Hospital. Dr Cehajic-Kaptenaovic was the first appointed NIHR Academic Clinical Fellow in ophthalmology in the UK. Her clinical interests lie in vitreo-retinal diseases and her research has focused on the development of an intravitreal approach of vector delivery for ocular gene therapy. Specifically, she has been looking at the effects of enzymatic degradation of extracellular matrix to enhance retinal transduction with the gene therapy vector, adeno-associated virus-2. This research was initiated during

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her Academic Clinical Fellowship and Masters in Investigative Ophthalmology and Vision Science and has continued into her PhD studentship, funded through prestigious MRC clinical research fellowship.

The fellowship evolved into investigations into the use of gene therapy to introduce optogenetic molecules (human opsins) into the retina and their ability to convert non-photoreceptor cells into photoreceptors. Jasmina has been awarded several prestigious prizes for this work including top research prize at the North Ophthalmological Society Meeting 2011; best research presentation the Academy of Medical Sciences Spring Meeting 2011, John Lee Prize 2013 from the Royal College of Ophthalmologists, Dickinson Trust Award 2013 from Central Manchester Foundation Trust, David McLeod Research Prize 2014 from Alcon, Keller Scholarship 2014 from the Royal College of Ophthalmologists and the MRC Centenary Award 2014. In addition Jasmina was awarded Retinitis Pigmentosa Fighting Blindness Award 2014 which allowed her to spend last year at Professor Flannary’s lab at the University of California in Berkeley to further develop optogenetic targeting of ON bipolar cells.

Restoration of Vision with Ectopic Expression of Human Rod Opsin

Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a nonselective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioural responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (~50–100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration.

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Dr Joseph CarrollMedical College of Wisconsin, USA

Joseph Carroll, PhD is the Richard O. Schultz, MD / Ruth Works Professor of Ophthalmology, and Professor of Biophysics and Cell Biology, Neurobiology & Anatomy at the Medical College of Wisconsin (MCW). After receiving his PhD in Cell & Developmental Biology from MCW in 2002, Dr. Carroll did his postdoctoral fellowship at the University of Rochester under the guidance of Dr David Williams. Here he developed expertise in the area of adaptive optics retinal imaging. In 2006, he joined the MCW faculty as an Assistant Professor in the Department of Ophthalmology.

Dr Carroll co-directs the Advanced Ocular Imaging Program (AOIP), which utilizes a variety of retinal imaging devices to study the structure and function of the living human retina with cellular resolution. The group has worked to develop novel image analysis tools to increase the scientific and clinical utility of these imaging devices, and has pioneered the dissemination of this technology to research groups around the world. Dr. Carroll and his team have been at the forefront of the clinical application of adaptive optics retinal imaging, with over 80 peer-reviewed publications. Patients from around the world travel to the program to participate in his studies on inherited retinal degenerations. His research is funded by multiple grants from the National Institutes of Health, as well as a number of public and private foundations.

Dr Carroll has received numerous awards, including the Wisconsin Association of Educational Opportunity Program Personnel - TRIO Achiever Award (2006), the UW Green Bay Outstanding Recent Alumni Award (2007), a Vision Research Award from the E. Matilda Ziegler Foundation (2007), a Research to Prevent Blindness Career Development Award (2008), a Young Investigator Award from the ALCON Research Institute (2012), and was named one of the “40 under 40” by the Milwaukee Business Journal (2014).

High-Resolution Retinal Imaging and Clinical Trials — What’s Next?

The human retina is a uniquely accessible tissue, and can be directly visualized using a variety of non-invasive imaging tools. The ability to image the living retina provides an implicit advantage in diagnosing and monitoring retinal disease, however the available resolution of conventional tools is limited. Adaptive optics (AO) enables correction of the eye’s monochromatic aberrations, and as a result provides nearly diffraction-limited imaging. Current systems are capable of imaging the smallest photoreceptor cells in the living retina. Moreover, significant cellular damage

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can exist in the presence of “normal” anatomy on conventional imaging modalities. Thus, there has been significant excitement surrounding the potential of using AO imaging tools in the context of emerging clinical trials for inherited retinal degenerations. In this talk, I will review the latest advances in AO imaging technology with a focus on the appearance of photoreceptors in retinitis pigmentosa, Stargardt disease, and achromatopsia. In particular, the relationship between photoreceptor anatomy as visualized with AO tools and that on conventional imaging modalities will be reviewed.

Dr Eric Pierce, Massachusetts Eye and Ear Hospital and Harvard Medical School, USA

Eric A. Pierce, M.D., Ph.D. is the Solman and Libe Friedman Associate Professor of Ophthalmology, Director of the Ocular Genomics Institute, Director of the Berman-Gund Laboratory for the Study of Retinal Degenerations, and Director of the Inherited Retinal Disorders Service in the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School. Dr. Pierce received his Ph.D. in Biochemistry from the University of Wisconsin-Madison and his M.D. from Harvard Medical School. He did his residency in Ophthalmology at Harvard and fellowship in Pediatric Ophthalmology at Children’s Hospital, Boston where he also took his first faculty position. He was then recruited to the Department of Ophthalmology at the University of Pennsylvania School of Medicine, where he was promoted to Associate Professor with tenure. He returned to Harvard in 2011 to establish the Ocular Genomics Institute. He became Director of the Berman-Gund Laboratory and Inherited Retinal Disorders Service in 2014. His research program is focused on understanding the molecular bases of inherited retinal degenerations, and developing gene and genetic therapies for these conditions.

Studies of the Genetic Causality of Inherited Retinal Degeneration

Inherited retinal degenerations (IRDs) are important causes of blindness. Even though IRDs are mostly monogenic, they are genetically heterogeneous with mutations in over 200 genes leading to disease. Despite substantial progress in sequencing and new disease gene discovery, current strategies can genetically solve only about 60% of IRD cases. Further, mutations in new disease genes are rare, and typically affect only a handful of IRD patients. This presentation will discuss our strategies for clinical diagnostic testing of patients with IRDs, and research studies to seek the apparently missing genetic causality for IRDs.

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Christina Fasser, Retina International

Christina Fasser is former CEO of Retina Suisse and president of Retina International as well as trustee of the Foundation “blindekuh” Switzerland

She began her career as an advertisement manager for international advertising agencies. From 1978 to 1990, she worked at the Swiss Federal Institute of Technology on various projects designed to aid the developing world, especially in the field of Food Science.

Affected by Retinitis Pigmentosa, Christina became involved in the RP Society as a founding member and has been its president from 1986 to 2004 and is still its CEO.

In 1992, she was elected president of Retina International (formerly the International Retinitis Pigmentosa Association). Retina International has at present over 30 member organisations, in which more than 300,000 individuals affected by retinal degenerative diseases are active. These organisations collect annually more than 30 million US dollars to be invested into research. In her capacity as president of Retina International, Christina is involved in promoting research on national and international levels and coordinating the efforts made by individual countries.

Christina Fasser has been a leading voice in the effort to focus attention on the need for scientific research to find a cure or treatment for retinal blindness for the past 25 years.

As President of Retina International, Christina works with the Management Committee to facilitate communication between members, researchers, industry and government, and to represent the member organisations at meetings world-wide.

In November 2011, Fighting Blindness lost one of its founding members, Mrs Geraldine Duggan. Those of us who knew Geraldine will remember her great wit, no-nonsense attitude and belief that supporting medical research was the best way to bring about a better quality of life for those affected by retinal degenerations. At every Annual General Meeting she would challenge Fighting Blindness and visiting researchers with the same question—the one on every parent and patient’s mind, “Yes that science is great, but when will we get a cure?” This is a thought that stays with us and drives us forward every year as we prepare for another Retina conference.Shortly before Geraldine’s death, Fighting Blindness’ first ever research project, one that she was instrumental in establishing, received an orphan drug designation. Geraldine was a warm welcoming person whose energy and enthusiasm for life was contagious. She gave great advice and always left our team filled with laughter. The staff and the board of Fighting Blindness wished to honour our great friend in 2012 by bestowing The Geraldine Duggan Award in her memory at the Retina Conference. The award, presented by Geraldine’s family, goes to a young investigator deemed to have presented the best abstract and poster to the meeting.

Thank you to the Duggan family for their on-going support of Fighting Blindness and the Retina Conference.Ar dheis Dé go raibh a hanam. Previous recipients of the Geraldine Duggan Award:

2012: Dr Alison Reynolds,University College Dublin

2013: Dr Sarah Chambers,Queens University, Belfast

2014: Dr Orla Galvin,University College Dublin

Twenty-eight abstracts, listed in the coming pages, were submitted for Retina 2015, the posters are available for viewing in the coffee/lunch area.

The Geraldine Duggan Award

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Geraldine Duggan’s daughters Suzanne and Olivia pictured at Retina 2013

Mrs Geraldine Duggan

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Poster List

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1. Rachel Moran, Waterford Institute of Technology Non-dietary Predictors of Plasma Lutein and Zeaxanthin

Concentrations in the Irish Population 2. Rebecca Power, Waterford Institute of Technology The Central Retinal Enrichment Supplementation Trial (CREST): Report 1.3. Conor Malone, Trinity College Dublin & Royal Victoria Eye and Ear Hospital Blue Cone Monochromatism Identified in an Irish Family4. Clare McClosely, St Vincent’s University Hospital, Dublin An Audit on the Time Tnterval from Diagnosis of Wet Age-Related Macular

Degeneration (ARMD) to Treatment Initiation with Anti-VEGF Intravitreal Injections5. Kirk Stephenson, Mater Misericordiae University Hospital, Dublin Target 5000: An Inherited Retinal Degeneration Registry6. Siobhan Eustace-Ryan, Dublin Institute of Technology A comparison of Testing Methodologies for the Detection of Mitochondrial Mutations Causing Leber’s Hereditary Optic Neuropathy.7. Andrew Smith, University College Dublin Identification of Novel Cone Photoreceptor-Enriched Factors

That Are Conserved in Zebrafish, Mouse and Human8. Stephen Carter, University College Dublin Functional investigations of cone-rod dystrophy associated with RAB289. Arpad Palfi, Trinity College Dublin miRNA Regulation in the R347 Mouse Retina, a Retinitis Pigmentosa Model10. Killian Hanlon, Trinity College Dublin Optimisation of AAV-Ndi1 for the Treatment of LHON11. Killian Hanlon, Trinity College Dublin Development of Retinal Ganglion Cell Promoters for AAV-mediated

Gene Therapies for LHON12. Daniel Manraj Maloney, Trinity College Dublin Development of a Mitochondrial Assay to Evaluate Novel Complex I Therapies.13. Alison O’Connor, University College Dublin Defective Photoreceptors Underlie Inherited Blindness in the Raifteirí Mutant14. Matthew Carrigan, Trinity College Dublin Target 5000: Population-scale Sequencing 15. Matthew Carrigan, Trinity College Dublin CHM and RPE65: A Diagnostic Paradox in a Choroideremia Pedigree16. Sarah Roche, University College Cork Changes in Retinal Architecture during Development and Degeneration

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17. Temmy Sasore, Conway Institute, University College Dublin Can Drug Combinations Targeting PI3K/Akt/mTOR Pathway Inhibit Angiogenesis,

Inflammation or Permeability in Human RPE and Endothelial Cell Lines?18. Stephanie Merrigan, University College Dublin Vitamin D Receptor Agonists Significantly Attenuate Ocular

Developmental Angiogenesis.19. Kayleigh Slater, Conway Institute, University College Dublin The Enhancement of Anti-Angiogenic Efficacy via Targeting

Multiple Signalling Pathways in vivo 20. Conor Daly, Conway Institute, University College Dublin Pharmacological Restoration of Visual Function in a Blind Zebrafish Mutant

Following Histone Deacetylase Inhibitor (HDACi) Treatment.21. Alison Reynolds, University College Dublin Phenotype-based Discovery Of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel

Inhibitor f Developmental and Pathological Ocular Angiogenesis22. Alice Wyse Jackson, University College Cork The synthetic Progesterone ‘Norgestrel’ is Neuroprotective in Stressed

Photoreceptor Cells, Mediating its Effects via Basic Fibroblast Growth Factor, Protein Kinase A and Glycogen Synthase Kinase 3β Signalling

23. Karl Kador, Biomedical Sciences Institute, Trinity College Dublin Tissue Engineered Transplantation to the Inner Neural Retina.24. Darrell Andrews, University College Dublin Targeting the Polycomb Repressor Complex chromatin remodeling

machinery for therapeutic benefit in Diabetic retinopathy25. Ana Ruiz-Lopez, University College Cork Neurotrophic Factor Profile in Retinal Cells and Explants Following Stress26. Ashleigh Byrne, Biosciences Institute, University College Cork The Synthetic Progestin Norgestrel acts to Increase LIF Levels

in the rd10 Mouse Model of Retinitis Pigmentosa27. Anna-Sophia Kiang, Trinity College Dublin Enhanced Drug Delivery to Rodent Retinas Following Inner Blood-Retina

Barrier Modulation.28. Kapil Dev, National University of Ireland, Galway Generation of Induced Pluripotent Stem Cells from Patients Harboring a RPE65

Mutation using a Mon-integrative Reprogramming Method

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Poster Abstracts

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1. Rachel Moran, Waterford Institute of Technology

Non-dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population

Rachel Moran, John Nolan, Jim Stack, Aisling M. O’Halloran, Joanne Feeney, Kwadwo O. Akuffo, Rose Ann Kenny, and Stephen Beatty

Objective: To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA).

Method: TILDA is a prospective cohort study of community dwelling adults aged 50 and over in the Republic of Ireland. Baseline demographic and health variables were collected during a face-to-face interview and a health assessment. Blood samples were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography and macular pigment (MP) optical density was measured using customized heterochromatic flicker photometry.

Results: After excluding participants with any eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with BMI, and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p<0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants with lower education (p<0.05, for all). Plasma L was significantly higher in subject reporting a family history of AMD, and in the group of ≥75 years old (p<0.05, for all). For each of these variables, the significant associations remained after controlling for the other variables.

Conclusion: The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.

Disclosures: Stephen Beatty and John Nolan are Directors of Nutrasight Consultancy Ltd, where they do consultancy work for companies with an interest in supplements for eyecare. All other authors report no potential conflict of interest. This work was supported by Bayer, Ireland and Waterford Institute of Technology Presidential Scholarship. TILDA is funded by the Irish Government, Atlantic Philanthropies and Irish Life plc.

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2. Rebecca Power, Waterford Institute of Technology

The Central Retinal Enrichment Supplementation Trial (CREST): Report 1.

Rebecca Power, John Nolan

Purpose: Macular pigment (MP), found at the central retina (macula), is comprised of the carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The Central Retinal Enrichment Supplementation Trial (CREST) is the first study to investigate the impact of supplementation with all three macular carotenoids on visual function in individuals with low MP (<0.56 ODU at 0.23°) and free of retinal disease, in the context of a large, double-blind, randomised clinical trial.

Methods: Subjects were randomly assigned to consume a formulation containing 10mg L, 2mg Z and 10mg MZ (active Group; n=48) or placebo (n=47). Data were collected at baseline, 3-, 6-, and 12-months. Contrast sensitivity (CS) at 6 cycles per degree (cpd) was the primary outcome measure. Secondary outcome measures included: CS at other spatial frequencies, best-corrected visual acuity, glare disability, photostress recovery, and light scatter. MP optical density (MPOD) was measured using dual-wavelength autofluorescence and serum carotenoid concentrations were analysed using high performance liquid chromatography.

Results: In the active group, a statistically significant improvement was detected in the primary outcome measure (CS at 6cpd: p=0.002, repeated measures analysis of variance). CS at 12 cpd also exhibited a statistically significant improvement in this group (p=0.004); these improvements equating to a gain of circa 3 letters on the Thomson test chart. In the active group, statistically significant increases were also detected in serum concentrations of L, Z and MZ (p<0.05, for all), in MPOD at 0.23° eccentricity and in MP volume (p<0.001, for both). For all the variables exhibiting statistically significant increases in the active arm, no such demonstrable change was noted in the placebo arm (p>0.05, for all).

Conclusion: Contrast sensitivity, an important measure of visual function, can be improved following supplementation with all three macular carotenoids, in a L:MZ:Z (mg) ratio of 10:10:2, in subjects with low MP and free of retinal disease. These findings have important implications for those endeavouring to maximise their visual performance and experience, whether for professional or leisure activities.

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3. Conor Malone, Trinity College Dublin & Royal Victoria Eye and Ear Hospital

Blue Cone Monochromatism Identified in an Irish Family

Authors: Conor Malone1, Matthew Carrigan2, Karen Collins1, Hilary Dempsey1, G. Jane Farrar2, Paul Kenna1, 2,

1)The Research Foundation, The Royal Victoria Eye and Ear Hospital, Dublin.2)The Ocular Genetics Unit, Trinity College, Dublin.

Next generation sequencing (NGS) has revolutionized our ability to identify disease-associated gene mutations and thus provide precise genetic diagnoses for patients with a wide variety of inherited retinal degenerations (IRD) and prepare them for possible therapeutic interventions. As part of our on-going efforts to contribute to a database of Irish IRD patients (Target 5000) a 73-year-old man, who presented with congenital visual impairment primarily related to day vision, was assessed at the Research Foundation at the Royal Victoria Eye and Ear Hospital, Dublin and was diagnosed with Achromatopsia on the basis of electroretinographic (ERG) features consisting of well-preserved rod-isolated responses combined with non-recordable cone-isolated responses. Two of the proband’s great nephews (sons of his sororal niece) were also found to have similar ERG patterns, thus strongly suggesting an X-linked mode of inheritance. Using NGS, the affected males were confirmed to have potentially pathological sequence variants in both the OPN1LW and OPN1MW gene clusters, (Xq28) mediating long-wavelength (‘red’) and medium wavelength (‘green’) cone opsin production respectively, refining the clinical diagnosis as blue cone monochromatism, an extremely uncommon IRD with a prevalence of approximately 1 in 100,000.

4. Clare McClosely, St Vincent’s University Hospital, Dublin

An Audit on the Time Tnterval from Diagnosis of Wet Age-Related Macular Degeneration (ARMD) to Treatment Initiation with Anti-VEGF Intravitreal Injections

C McCloskey, N Horgan

Objectives: Assess interval from diagnosis to treatment of wet ARMD, with recommended standard of care. The Royal College of Ophthalmologists(RCOphth) initially recommended a time interval of six weeks. With increasing pressures to deliver treatment sooner, recently published guidelines recommend two weeks.(1)

Method: Patients who attended for intravitreal injections during October 2013 were documented from an Attendance Record. Viewing medical records and excluding diagnoses other than ARMD, the remaining sample size was 32. Working retrospectively from date of first injection, date of diagnosis was determined and time interval calculated. Results: In reference to the original guidelines(six weeks), 28(87.5%) patients received the recommended standard of care and 4(12.5%) patients fell outside this advised time interval. The sample of patients on whom this audit was based, involved injections administered between 2010 and 2013.

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Conclusions: 28(87.5%) patients met the recommended standard of care according to the guidelines at the time. New guidelines published in September 2013, recommend a period of two weeks from diagnosis and even propose administering the first anti-VEGF injection on first presentation.(2) Applying the data from this audit to these guidelines shows that 14(44%) patients received intravitreal injections within the recommended time period while 18(56%) patients did not.

Recommendations: With increasing evidence showing delays in treatment can dramatically reduce visual outcomes,(3) ensure all staff in the Ophthalmology Department are familiar with the new guidelines. Aim to schedule patients for their first treatment injection as soon as possible from date of diagnosis. Following this, a re-audit in 12months to assess progress since September 2013.

5. Kirk Stephenson, Mater Misericordiae University Hospital, Dublin

Target 5000: An Inherited Retinal Degeneration Registry

Kirk Stephenson, David Keegan

Background: Historically, there have been no effective treatments for Inherited Retinal Degenerations, such as Retinitis Pigmentosa and Stargardt’s disease. No database has been kept of people living in Ireland with these conditions. As new research unveils novel therapies, it becomes increasingly relevant that a registry of such patients be created. We estimate that 2500 to 3000 people in Ireland are affected. With detailed phenotypic and genotypic data, we can identify eligible patients for involvement in trials of novel clinical therapies.

Methods: Referrals are accepted from ophthalmologists, general practitioners, and optometrists throughout Ireland. Anyone with early or adult onset severe retinal degenerations may be included, provided they are able to give informed consent. Phenotyping, performed at the Mater Misericordiae University Hospital, involves taking a personal and family history, in addition to ocular examination including fundal photographs. Genotyping is performed by the Trinity College Dublin genomics laboratory and validated by the Manchester Centre for Genomics.

Results: Over eighty patients have been registered through our facility. The clinical phenotype of each patient has been documented, and genetic testing is gradually returning from the validated laboratory. Individuals with a variety of inherited retinal degenerations have been recruited, including: retinitis pigmentosa, Usher’s Syndrome, and Stargardt’s disease. Family data has uncovered novel genetic variants, in particular for foveal schisis. This information is of much clinical significance internationally, due to Irish emigration to all corners of the globe.

Conclusions: The genetic data available so far shows a mixture of known mutations and previously unknown variants. We can guide affected individuals into therapeutic trials at international centres of excellence. For novel mutations in sufficient volume, we aim to instigate therapeutic trails within Ireland. Our goal is to making disease-modifying treatments available to these patients and future generations. A comprehensive registry of people with inherited retinal degenerations is vital to this plan.

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6. Siobhan Eustace-Ryan, Dublin Institute of Technology

A comparison of Testing Methodologies for the Detection of Mitochondrial Mutations Causing Leber’s Hereditary Optic Neuropathy.

Siobhan Eustace-Ryan , Derek Neylan, Veronica O’Dwyer

Leber’s Hereditary Optic Neuropathy (LHON; MIM 535000) is one of the more commonly inherited optic neuropathies with a worldwide incidence of approximately 1 in 31,000. It results in significant visual morbidity among young adults, with a peak age of onset typically between the ages of 15–30. 95% of all LHON patients will have one of 3 primary mitochondrial mutations, G3460A (A52T of ND1), G11778A (R340H of ND4) and T14484C (M64V of ND6). Visual recovery can occur in some LHON patients but the extent of the visual recovery is influenced by which mutation is involved in the development of that patient’s LHON. Thus, an accurate mutation detection strategy can have a significant prognostic value to the LHON patient.

The 3 primary mutations are typically identified by individual end-point PCR-RFLP, allele specific PCR or individual targeted bi-directional Sanger sequencing reactions. This study aimed to evaluate simplex PCR-RFLP, ARMS PCR and bi-directional Sanger sequencing with regard to reliability, costs and hands on time. A novel multiplex PCR-RFLP was designed to detect the 3 primary mutations in a single tube format that offers an advantage over current testing methodologies with regard to costs, time, the ability to detect heteroplasmy and robustness. In addition, we developed a series of synthetic cloned controls that offer an unlimited patient free resource of LHON controls applicable to all current testing algorithms.

In conclusion, we developed a simple cost effective assay to detect 95% of LHON causing mutations and developed a set of cloned controls providing an unlimited patient free resource for LHON testing.

7. Andrew Smith, University College Dublin

Identification of Novel Cone Photoreceptor-Enriched Factors That Are Conserved in Zebrafish, Mouse and Human

Andrew Smith, Breandán Kennedy

The inability of the retina to detect/transmit light-triggered signals is largely responsible for incurable blinding conditions such as age-related macular degeneration, and cone-rod dystrophy, due to dysfunction or death of photoreceptor cells. Cone photoreceptors mediate colour vision and high visual acuity under brighter light conditions. Notably, our understanding regarding i) factors regulating cone photoreceptor differentiation from retinal progenitor cells, and ii) factors maintaining cone photoreceptor survival remains limited.

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Microarray analysis of flow-sorted cone photoreceptors from the transgenic zebrafish line Tg(gnat2:EGFP) identified cone-enriched factors. RNAseq data of photoreceptors of the cone dominant Nrl -/- mouse and rod dominant Nrl GFP mouse were compared to identify evolutionarily conserved cone-enriched factors. Human retinal RNAseq data was analysed to confirm evolutionary conservation, and retinal enrichment. Genes were ranked based on their cone enrichment. PCR was performed in wild type (Tü) zebrafish eyes to confirm expression of highest-ranking cone-enriched factors during development. The identification of these novel factors has informed the development of morpholino mediated knockdown, and CRISPR-Cas9 mediated knockout models of genes of interest. 27 novel, evolutionarily conserved, cone-enriched genes were identified in zebrafish and mice, using microarray, and RNAseq analysis, respectively. This work will aid in the development of CRISPR/Cas-9 mediated knockout zebrafish and mouse models to understand the role these genes play in the development, function, and survival of cone-photoreceptors. This will inform future drug discovery efforts to identify compounds which promote the survival of cone-photoreceptors.

8. Stephen Carter, University College Dublin

Functional investigations of cone-rod dystrophy associated with RAB2

Stephen Carter, Breandan Kennedy

RAB28 is a member of the RAS superfamily of small GTPases which has recently been linked to a form of autosomal recessive cone-rod dystrophy (CRD); an inherited disorder whereby the photoreceptors of the retina begin to degenerate and die, resulting in permanent blindness. Localisation of rat RAB28 to the base of the connecting cilium (CC) of photoreceptors suggests a possible role for RAB28 in cilia. Cilia are sensory organelles which are present on the surfaces of most cell types. In photoreceptors, the cilium is modified to form the outer segment, where light detecting opsins are localised. Blindness is often a feature of disorders which affect the cilium, known as ciliopathies.

We are taking a dual-model approach in dissecting the molecular function of RAB28, combining the genetic tractability of C. elegans and the vertebrate biology of zebrafish. We are also making use of the novel genome editing technology CRISPR to generate a zebrafish knockout model of Rab28 associated CRD. This will allow us to understand the role of RAB28 in cilia generally and in photoreceptors specifically, as well as the pathomechanism of its associated disorder.

In C. elegans, a Prab-28::gfp promoter fusion is expressed in ciliated sensory neurons and GFP-tagged RAB-28 localises to the cilium, undergoing a ciliary transport process known as intraflagellar transport (IFT). This transport is disrupted by mutations in the IFT machinery. Despite this association, behavioural and microscopy based assays used to assess C. elegans ciliary mutants have so far shown that rab-28 -/- worms have no obvious ciliary defects. Neither has a genetic interaction so far been found between rab-28 and two other ciliary GTPase genes, arl-3 and arl-13. We are currently also testing the efficiency of CRISPR constructs targeting zebrafish rab-28 at creating a gene edit.

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9. Arpad Palfi, Trinity College Dublin

miRNA Regulation in the R347 Mouse Retina, a Retinitis Pigmentosa Model

Arpad Palfi, Karsten Hokamp, Stefanie M. Hauck, Sebastian Vencken, Sophia Millington-Ward, Naomi Chadderton, Marius Ueffing, Catherine Greene, Paul Kenna, Jane Farrar

Respiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Dublin 9, Ireland

Research Unit Protein Science, Helmholtz Zentrum Munchen - German Research Center for Environmental Health (GmbH), Neuherberg, Germany

Center for Ophthalmology, Institute of Ophthalmic Research, University Tubingen, Tubingen, Germany

AbstractWe found changes in levels of miR-1, miR-133, miR-142, miR-96, miR-182 and miR-183 in the retina of the RHO-347+/-Rho+/- (R347) mouse; a model for rhodopsin-linked retinitis pigmentosa. In this study, we aimed to identify proteins, whose expression is regulated by the above miRNAs. The strategy was to compare the proteome of the R347 and wild type (wt) mouse retinas, and relate this to altered expression of predicted targets for these miRNAs. In silico analysis was used to predict miR targets. Protein levels from retinas of 1-month R347 and wt mice were analysed by label free LC-MS/MS. An in vitro 3’-UTR assay was used to analyse the interaction between target mRNA and miRNAs. miRNA capture was used to demonstrate direct mRNA-miRNA interactions in vivo. LC-MS/MS was used to identify 1446 gene IDs in the samples. From the predicted targets, 538 were detected by LC-MS/MS. 23, 10, 6, 35, 41 and 18 potential target genes were identified for miR-1, miR-133, miR-142, miR-96, miR-182 and miR-183, respectively.

A notable candidate, Rac1, was selected for further exploration. Rac1 protein level increased to 339.9±24% (p<0.001) in R347 vs. wt retinas. The Rac1 3’-UTR contains a highly conserved overlapping binding site for miR-96/miR-182 and the level of these miRNAs decrease by approx. 50% in the R347 vs. wt retina. A 3’-UTR assay with the Rac1 3’-UTR demonstrated approx. 50% suppression (p<0.001) by both miR-96 and miR-182 in vitro. miRNA capture was performed on fixed wt retinas; Rac1 mRNA was enriched by 50.0 ±9.4 fold (p<0.01), while miR-96 and miR-182 levels demonstrated a combined increase of approx. 8.7-fold (p<0.05), providing evidence that these miRNAs are in direct physical contact with the Rac1 mRNA. Results indicate that Rac1 expression is co-regulated by miR-96 and miR-182 in the mouse retina, providing a link between miRNA regulation and Rac1 pathways.

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10. Killian Hanlon, Trinity College Dublin

Optimisation of AAV-Ndi1 for the Treatment of LHON

Killian S. Hanlon*, Naomi Chadderton*, Matthew Carrigan, Sophia Millington-Ward, Arpad Palfi, Paul F Kenna and G Jane Farrar.

School of Genetics & Microbiology, Trinity College Dublin* These authors contributed equally

Leber Hereditary Optic Neuropathy (LHON) is a mitochondrially inherited eye disorder involving mutations in subunits of the mitochondrial respiratory complex I. LHON affects approximately 1 in 30,000 people and involves sudden, rapid degeneration of RGCs, optic nerve atrophy and subsequent loss of central vision. LHON represents an unmet clinical need, with therapeutic development impeded by the heterogeneity seen in populations and the need to deliver the therapy to hundreds of mitochondria per cell. Ndi1 encodes a single yeast protein that replaces the function of complex I. We have previously shown that wild-type Ndi1, when delivered via a single intravitreal injection of a recombinant AAV vector, can provide significant benefit in a rotenone-induced mouse model of LHON, thus providing a mutation independent therapy for the disorder.

In the current study Ndi1 has been optimised to increase levels of expression. Ndi1 constructs with humanised codon usage profiles (which differ significantly from yeast) have been generated and shown to provide higher expression of Ndi1 in the mouse retina when delivered using AAV2. Increased levels of expression were confirmed by Western blot analysis compared to AAV2 expressing the native Ndi1. Optimised AAV2-Ndi1 has also been assessed for functionality in vivo in both wild-type mice and the rotenone mouse model via intravitreal injection, and compared to the native Ndi1. Conservation of visual function was examined using behavioural tests to measure the optokinetic reflex and demonstrated that a lower dose of optimised Ndi1 provides superior protection to the retina than wild-type Ndi1 against rotenone insult. Further, histological analysis of retina and optic nerve showed the benefit of optimised Ndi1. Optimised Ndi1 thus offers a refined therapy with substantial therapeutic value that may, in principle, be achieved using a significantly decreased viral load compared to the native Ndi1 therapy.”

11. Killian Hanlon, Trinity College Dublin

Development of Retinal Ganglion Cell Promoters for AAV-mediated Gene Therapies for LHON

Killian S. Hanlon*, Sophia Millington-Ward*, Naomi Chadderton, Arpad Palfi, Pete Humphries, Paul F Kenna and G Jane Farrar.

School of Genetics & Microbiology, Trinity College Dublin* These authors contributed equally

Leber Hereditary Optic Neuropathy (LHON) is a mitochondrially-inherited disorder that results in bilateral loss of retinal ganglion cells (RGCs), caused by mutation in any of

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several mitochondrial complex I respiratory proteins. We have previously shown that Ndi1 – a yeast protein that functions in place of complex I – has been shown to be effective in preserving RGCs in an LHON mouse model, when administrated using an AAV vector. While current Ndi1 vectors use a non-specific promoter to drive expression, localising Ndi1 expression to the ganglion cell layer (GCL) would represent a significant optimisation of the approach. The packaging size of AAV (4.7kb) imposes a limit on the size of usable promoters and genes. To our knowledge, no tissue-specific promoter sequence has been defined that is sufficiently small in size for AAV-mediated gene expression in RGCs. We examined genes with expression profiles limited to the GCL to determine potential promoter sequence conservation. Conservation of sequence across mammalian species was used as a proxy for putative function. One of these sequences, termed Ganglion cell promoter 1 (GCL1), showed promise and was engineered into an AAV2 virus expressing EGFP.

Here we demonstrate the effectiveness of GCP1 in localising EGFP expression to the GCL when administered via intravitreal injection. Furthermore, absence of EGFP expression was demonstrated when targeted towards photoreceptors via subretinal injection, verifying the tissue-specific nature of GCP1. Expression of AAV2.GCP1-EGFP was compared to dose-matched expression from a non-specific promoter construct, AAV2.CMV-EGFP. GCP1-EGFP was shown to provide equivalent expression to CMV-EGFP in the GCL. GCP1 thus offers a tissue-specific promoter option for therapies targeted toward RGCs. Its size allows for the deployment within AAV vectors and the potential to target therapeutic gene expression to RGCs without compromising functionality. GCP1 is thus a valuable addition to the expanding gene therapy toolbox.

12. Daniel Manraj Maloney, Trinity College Dublin

Development of a Mitochondrial Assay to Evaluate Novel Complex I Therapies.

Daniel Manraj Maloney, Naomi Chadderton, Sophia Millington-Ward & G Jane Farrar

Many neurological and physiological disorders are characterized by mitochondrial dysfunction due to the accumulation of mutations affecting both the mitochondrial and nuclear genomes. These include Alzheimer’s disease, multiple sclerosis (MS), age-related macular degeneration (AMD) amongst other disorders. These disorders have a common pathology where mitochondrial dysfunction leads to a lack of energy production and ultimately the death of the cell. The type of cell affected by this dysfunction affects the pathology of the disease. For instance if a spinal neuron suffers this dysfunction it can lead to MS, whereas if a retinal ganglion cell suffers it can lead to diseases such as Leber’s Hereditary Optic Neuropathy (LHON). These observations have prompted interest in exploring innovative therapeutics to modulate mitochondrial disorders which frequently involve complex I deficiency. The Farrar laboratory has explored gene therapies for ocular disorders such as LHON using Ndi1, a yeast gene which is a complex I homologue.

In order to test the efficacy of Ndi1 and subsequent refinements, amongst other potential therapies, we have developed a robust, empirical assay of mitochondrial function. Previous assays used the level of NADH oxidation in a sample both before and after rotenone as a measure of complex I activity. To optimally distinguish between the

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activity of complex I and the therapeutic, the assay was modified with the addition of a second inhibitor which allowed specific measurement of the therapeutic, in this case Ndi1. As this is an in vitro assay, it allows large scale screening of potential therapeutics and ensures only those that show strong evidence of efficacy are then tested in vivo. In combination with other quantitative assays such as Reactive Oxygen Species generation, this allows detailed evaluation of the health of mitochondria within a sample and thereby demonstrates the benefit of a potential therapeutic modality.

13. Alison O’Connor, University College Dublin

Defective Photoreceptors Underlie Inherited Blindness in the Raifteirí Mutant

A. O’Connor ; B. Sapetto-Rebow; L. Shine; S. McLoughlin; D. Cottell; M. Taylor; Y. Alvarez; B. N. Kennedy; AL. Reynolds

Purpose: To characterise the basis of the inherited visual function defect in the Raifteirí mutant.

Methods: Optokinetic response (OKR) screens were performed on N-ethyl-N-nitrosourea (ENU)-mutagenised zebrafish to identify families with recessive defects in visual function. Retinal morphology was characterised by microscopy and immunohistochemistry using retinal cell-specific markers. Apoptosis levels were determined by TUNEL staining. Circadian behaviours were ascertained using Zebralab (Viewpoint). Electroretinograms were recorded. Linkage analysis was performed using a standard zebrafish mapping panel.

Results: A novel mutant designated Raifteirí (raf) was identified by OKR screens. Raf mutants show no visual response and are paler with slightly smaller eyes. Locomotor activity levels are ~50% of normal siblings however raf mutants exhibit circadian behaviour and a shadow response. No difference in apoptosis is observed between mutants and siblings. Light microscopy and DAPI staining show raf mutants to have normal retinal lamination. Staining of the inner retina suggests that cell differentiation is equivalent in siblings and mutants. In contrast, staining of the outer retina with photoreceptor-specific markers shows an absence of rod photoreceptors in all but peripheral retina. In addition cone photoreceptors appear stunted and there is a reduction in outer segment staining in raf mutants. Electron microscopy data shows the presence of a small number of stunted outer segments in the central retina of raf mutants. Raf mutants show no electrophysiologial response at lower light intensities and a tiny, latent response at higher flash intensities. The raf gene has been mapped to a marker on the proximal part of zebrafish linkage group 23.

Conclusions: We have identified and partially characterised a novel zebrafish model of inherited blindness. Electroretinographic and histological analyses suggest that specific defects in raf outer retina underlie loss of visual function. A number of interesting candidate genes lie on linkage group 23, which are currently being sequenced.

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14. Matthew Carrigan, Trinity College Dublin

Target 5000: Population-scale Sequencing

Authors: Matthew Carrigan, Emma Duignan, Pete Humphries, Andrew Green, David Keegan, Paul Kenna, G. Jane Farrar

Target 5000 (T5000) is an ongoing next-generation sequencing (NGS) project to identify the mutations causing retinal disease (RD) in Irish patients. 286 pedigrees comprising 501 individuals have now been sequenced as part of the T5000 project, using a targeted gene panel strategy. Of the 286 pedigrees thus far analysed, a candidate causative mutation has been identified in 166 pedigrees (58%). The analysis for many of these pedigrees has now progressed to confirmatory Sanger sequencing. Multiple novel mutations in known RD genes have been identified and confirmed by Sanger sequencing during the course of the study. Notably, the GNAT1 gene has been implicated in retinitis pigmentosa for the first time (Carrigan et al 2015, in press), having previously only been implicated in congenital stationary night blindness (CSNB).

The T5000 study represents the first comprehensive population-level survey of the mutations causing retinal degeneration in the Republic of Ireland. The results of the T5000 study will potentially enable patients to access the growing number of clinical trials for gene therapies and other mutation-specific treatments, and will enable researchers to focus on treatments that will benefit the greatest numbers of patients. 15. Matthew Carrigan, Trinity College Dublin

CHM and RPE65: A Diagnostic Paradox in a Choroideremia Pedigree

Authors: Matthew Carrigan, Emma Duignan, Paul Kenna, G. Jane Farrar

Choroideremia is an inherited X-linked retinal condition caused by mutations in the CHM gene which results in progressive loss of visual function. We report here a case of a choroideremia pedigree with a well-characterized premature stop mutation in the CHM gene shared by some but, unexpectedly, not all affected members of the family. Next-generation sequencing of an affected member of the pedigree who did not carry the CHM mutation revealed that this individual had a novel homozygous stop mutation in the RPE65 gene. Recessive mutations in the RPE65 gene are known to be causative of Leber’s congenital amaurosis (LCA) and can cause a form of autosomal recessive retinitis pigmentosa with choroidal involvement, which has been reported to masquerade as choroideremia in the past. This is therefore an extremely rare case of an RD pedigree with two distinct causative mutations in two separate genes, which coincidentally lead to very similar clinical phenotypes. This finding highlights the ability of next-generation sequencing to provide novel, unexpected and clinically-relevant information which would be opaque to other diagnostic methods.

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16. Sarah Roche, University College Cork

Changes in Retinal Architecture during Development and Degeneration

Sarah L. Roche, Alice C. Wyse Jackson, Ashleigh M. Byrne, Ani M. Ruiz Lopez

and Thomas G. Cotter*

Cell Development and Disease Laboratory, Biochemistry Department, Biosciences Institute, University College Cork, Cork, Ireland.

Purpose: To study postnatal development of the rd10 retina, a mouse model of retinitis pigmentosa.

Methods: Rd10 mice and age-matched C57 control mice were taken at postnatal day (P)5, P10, P15, P20, and P25 to study postnatal development of the retina. Three mice of each genotype and age were used. Eyes were enucleated and sectioned at 7µm. Using fluorescence microscopy and a panel of well-characterised antibodies for identifying retinal cells and structures, rd10 retinas were studied for any developmental abnormalities compared to C57 controls.

Results: We report on novel findings that the mutation in the rd10 mouse results in retinal abnormalities earlier than was previously thought. Although the mutation is present in rods, we have shown that defects in rod outer segments, bipolar cells and amacrine cells, altered synaptic connectivity in photoreceptors, as well as reduced vasculature are present in the retina prior to the loss of photoreceptors. Additionally, we observe a dramatic response of glial cells during this period. Microglia, the resident macrophages of the retina, respond as early as P5, ~13 days before any photoreceptor loss is detected, with Müller glia and astrocytes exhibiting changes from P15. These results show that a gliotic response precedes photoreceptor loss, and could be a determining factor in the fate of these cells.

Conclusions: Overall, these findings contribute significantly to our understanding of disease onset and progression in the rd10 mouse. In particular, we highlight a potential role for glial cells in exacerbating the rate of photoreceptor death. These findings will need to be considered when designing and trialling potential treatments for RP using this mouse model, as cell types other than photoreceptors appear to be affected prior to and during the period of photoreceptor loss.

We are grateful to Fighting Blindness Ireland and Science Foundation Ireland for supporting this work.

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17. Temmy Sasore, Conway Institute, University College Dublin

Can Drug Combinations Targeting PI3K/Akt/mTOR Pathway Inhibit Angiogenesis, Inflammation or Permeability in Human RPE and Endothelial Cell Lines?

Temmy Sasore, Breandán Kennedy

Age-related macular degeneration (AMD), diabetic retinopathy (DR) and diabetic macula edema (DME) are characterised by inflammation, retinal angiogenesis and increased retinal vascular permeability (RVP). There is an urgent need to develop better therapies to treat these diseases. Previously, we showed that combinations of PI3K/Akt/mTOR (PAM) pathway inhibitors have additive or synergistic anti-angiogenic activity in vivo (Sasore and Kennedy 2014). Here, we assess the anti-angiogenic, anti-inflammatory or anti-RVP of these drugs in human RPE and endothelial cells.

PAM pathway target genes (PIK3CA, PIK3R1, AKT1, MTOR, RPS6KB1 and EIF4EBP1) are expressed in human ARPE-19. The most active drug combinations additively inhibit phosphorylation of p70S6K protein in human RPE cells. Preliminary data indicate that individual PAM pathway drugs reduce sVCAM-1 expression, with drug combinations having stronger effects. These drugs also reverse barrier disruption induced in ARPE-19 cells as determined by localization of ZO-1. In HMEC-1 cells, these combinations also inhibit in vitro tubule formation.

In summary, our study identifies combinations of PI3K/Akt/mTOR pathway inhibitors that are effective inhibitors of angiogenesis and cellular permeability in vitro. Further studies will evaluate the effect of these drugs on inflammation and permeability using multiplex ELISA and trans-epithelial/endothelial electrical resistance (TEER), respectively. In parallel, the activity of these drug combinations will also be assessed in mouse model of developmental angiogenesis. Therefore, further investigations of the PI3K pathway and drug combinations hold promise as inhibitors of retinal angiogenesis, inflammation and retinal vascular permeability.

18. Stephanie Merrigan, University College Dublin

Vitamin D Receptor Agonists Significantly Attenuate Ocular Developmental Angiogenesis.

Stephanie Merrigan, Orla Galvin, Alison Reynolds and Breandán Kennedy.

School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin.

Angiogenesis is a pivotal process in development and disease. Pathological ocular angiogenesis can ultimately cause blindness in diseases such as neovascular age related macular degeneration (nAMD). Current gold-standard nAMD therapeutics are associated with resistance, repeated intra-ocular injections, high costs and adverse reactions. Therefore, a clinical need remains to develop improved therapies with greater efficacy and safety profiles.

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A phenotype-based screen of the ICCB Known Bioactives Library was performed to identify a novel safe small molecule inhibitor of ocular angiogenesis. Compounds were screened for inhibition of ocular hyaloid vessel (HV) and trunk inter-segmental vessel (ISV) development in Tg(fli1:EGFP) zebrafish larvae. The biological active form of vitamin D “Calcitriol” represents a lead hit. Calcitriol and several vitamin D receptor agonists (VDRA) significantly inhibited ocular developmental angiogenesis by up to 50%. Vitamin D receptor (VDR) expression was analysed by RT-PCR and found to be present in the eye and trunk of larvae. Several miRNA have shown differential expression in larvae in response to Calcitriol treatment. Here, we show miRNA 21 to be upregulated in the eye of Calcitriol threated larvae.

Safety studies used light microscopy to evaluate retinal morphology and the optokinetic response (OKR) assay to assess visual function in response to treatment. VDRAs had an adverse effect on larval OKR despite normal retinal lamination/morphology. Human retinal pigment epithelial cell (ARPE-19) viability by MTT, human retinal endothelial cells (ACBRI 181) tubule formation and mouse aortic ring sprouting angiogenesis in response to treatment was quantified. ARPE-19 cells show dose-dependent cytotoxicity to VDRAs, tubule formation in ACBRI 181 cells was unaltered by VDRAs and preliminary data shows VDRAs to reduce aortic ring sprouting.

Here, we demonstrate that VDRAs significantly and specifically inhibit ocular angiogenesis during zebrafish development. Future experiments will evaluate the molecular mechanisms of VDRAs anti-angiogenic activity and their efficacy in pre-clinical mouse models.

19. Kayleigh Slater, Conway Institute, University College Dublin

The Enhancement of Anti-Angiogenic Efficacy via Targeting Multiple Signalling Pathways in vivo

Kayleigh Slater, Breandan Kennedy

Ocular neovascularisation is a pathological hallmark common to a number of debilitating ocular diseases including diabetic retinopathy and age-related macular degeneration. Current therapies include the use of anti-VEGF monoclonal antibodies. Unfortunately, the high financial cost, lack of efficacy and need for frequent intraocular injections associated with anti-VEGF therapies mean that alternative therapies are required. A number of signalling pathways including the MAPK/ERK, Sonic Hedgehog (Shh), Wnt, and the PI3K/AKT/mTOR pathways are known to be upregulated in ocular neovascularisation. Using drug combinations that target multiple signalling pathways may allow for enhanced efficacy and reduced toxic effects due to the requirement for decreased drug concentrations.

The intersegmental vessel assay was performed in Tg(fli1:EGFP) zebrafish to determine the anti-angiogenic efficacy of compounds based on their ability to inhibit intersegmental vessel growth in comparison to a vehicle control (n=3, N=30). Similarly, the hyaloid vessel assay was conducted to elucidate the efficacy of drug combinations based on number of primary branches inhibited (n=3, N=30).

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The efficacy of various drug treatments; both individually and in combination, for the treatment of angiogenesis were evaluated. The small molecule inhibitors were ranked in order of efficacy and the highest ranking drugs were chosen to be tested in combination (Sorafenib, Cyclopamine, Palomid 529 and TAK 733).

These small molecule inhibitors that target pathways known to be involved in ocular angiogenesis were shown to have significant anti-angiogenic efficacy in both assays. Combinations of the highest ranking drug compounds had significant anti-angiogenic effects in the zebrafish developmental angiogenesis assays.

20. Conor Daly, Conway Institute, University College Dublin

Pharmacological Restoration of Visual Function in a Blind Zebrafish Mutant Following Histone Deacetylase Inhibitor (HDACi) Treatment.

Conor Daly, Breandán Kennedy

Background: Controversially, pharmacological inhibition of Histone Deacetylase (HDAC) proteins is in clinical trial for the treatment of inherited retinal degenerations. Previous studies report that patients suffering from the inherited retinal degeneration Retinitis Pigmentosa (RP) may show improved visual field and acuity following treatment with the HDAC inhibitor valproic acid (VPA). Utilising zebrafish models of retinal degeneration we rescued retinal morphology and visual function of a blind zebrafish mutant (dye mutant) by treatment with HDACi.

Methods:Visual function was assessed by Optokinetic Response (OKR) and Visual Motor Response (VMR) assays. Cone photoreceptor outer segment (OS) morphology, cilliary marginal zone (CMZ) apoptosis and cone photoreceptor outer segment (OS) length were assessed by light microscopy. Larvae were drug treated with HDACi (1 µM TSA, 10 µM MC1568 and 10 µM MS275) with or without 100-500 nM ANA-12 from 3-5 dpf at 28.5 C. An unbiased shotgun proteomic analysis of TSA-treated dye eyes was carried out by LC-MS/MS and the resulting dataset analysed by Ingenuity Pathway Analysis (IPA) software.

Results: The dye mutant has reduced visual behaviour and several defects in retinal morphology compared to sibling larvae. HDACi treatment of dye results in improved OKR and VMR, rescue of gross morphological defects, an 80% decrease in the number of dead cells in the CMZ and an increase in cone photoreceptor OS length. Proteomic analysis identified significantly differentially expressed proteins in response to treatment, and pathway analysis identified Bdnf as a major contributing mechanism to rescue. ANA-12 treatment blocks Bdnf/Trkb signaling and HDACi meditaed rescue in dye.

Conclusions: HDAC inhibition is effective in restoring visual function and rescuing morphological defects in a zebrafish model of retinal degeneration.

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21. Alison Reynolds, University College Dublin

Phenotype-based Discovery Of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Inhibitor f Developmental and Pathological Ocular Angiogenesis

Alison Reynolds, Breandan Kennedy

Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularisation.

Phenotype-based chemical screens were performed using the ChemBridge Diverset™ library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. Hit compounds were tested in mammalian models of angiogenesis. A structural activity relationship (SAR) study was performed and structurally related compounds tested in zebrafish and where efficacious, mammalian models of angiogenesis.

2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4-10 µM in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants and retinal revascularisation in OIR mice. Quininib are structurally related compounds are well tolerated in zebrafish, human cell lines and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed quininib does not directly target VEGF receptors but antagonises cysteinyl leukotriene receptor 1 (CysLT1) with an IC50 of ~1.4 µM. Approximately 15 closely related compounds have also shown efficacy in angiogenesis models.

In summary, quininib is a novel anti-angiogenic small molecule CysLT1 antagonist. Quininib inhibits developmental and pathological angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT1. Quininib has potential as a novel therapeutic to treat ocular neovascular pathologies and may complement current anti-VEGF biologicals.

22. Alice Wyse Jackson, University College Cork

The synthetic Progesterone ‘Norgestrel’ is Neuroprotective in Stressed Photoreceptor Cells, Mediating its Effects via Basic Fibroblast Growth Factor, Protein Kinase A and Glycogen Synthase Kinase 3β Signalling

Alice C. Wyse Jackson, Thomas G. Cotter

Cell Development and Disease Laboratory, Biochemistry Department, Bioscience Research Institute, University College Cork, Cork, Ireland

Purpose: To determine the cellular mechanism and examine the downstream signalling pathways associated with the neuroprotective compound ‘Norgestrel’ both in vitro and ex vivo.

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Methods: 661W cone photoreceptor cells were serum starved over 24 hours and assayed for cellular viability by the MTS assay. Cells were analysed by western blotting for characteristic apoptotic proteins (PARP, Caspase 3) and further cell analysis for bFGF expression in response to Norgestrel was carried out by western blotting, ELISA and rt-qPCR. Specific siRNA knock down for bFGF and analysis of associated signalling pathways was determined by western blotting and inhibitor studies. C57BL/6 retinas were explanted and treated with nitric oxide inhibitor sodium nitroprusside (SNP) to induce apoptosis. Explants were then treated with PKA pathway inhibitor H-89 and cell death was assayed by TUNEL.

Results: Norgestrel showed significant neuroprotective effects in stressed photoreceptors over 24 hours, reducing apoptosis from 40% to 10% through inhibition of PARP and Caspase 3 cleavage. We hypothesised that Norgestrel may act through the upregulation of basic fibroblast growth factor (bFGF). In vitro analysis revealed a significant increase in bFGF levels in response to Norgestrel over 6 hours. Specific siRNA knock down of bFGF abrogated the protective properties of Norgestrel. Furthermore, Norgestrel mediated a bFGF-dependent inactivation of glycogen synthase kinase 3β (GSK3β) through phosphorylation at serine 9. The effects of Norgestrel on GSK3β were dependent on Protein Kinase A (PKA) pathway activation for specific inhibition of both the PKA and GSK3β pathways prevented Norgestrel-mediated neuroprotection of stressed photoreceptor cells in vitro. Involvement of the PKA pathway following Norgestrel treatment was also confirmed through an ex vivo model of retinal degeneration.Conclusions: These results indicate that the protective efficacy of Norgestrel is due to the bFGF-mediated activation of the PKA pathway, with subsequent inactivation of GSK3β. This work was kindly supported by Fighting Blindness Ireland and Science Foundation Ireland.

23. Karl Kador, Biomedical Sciences Institute, Trinity College Dublin

Tissue Engineered Transplantation to the Inner Neural Retina.

Karl E. Kador1,2, Monisha Malek1 and Jeffrey L. Goldberg1,3

1Shiley Eye Center and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA USA; 2Current Address: Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland; 3Current Address: Byers Eye Institute, Stanford University, Palo Alto, CA USA.

The lack of regeneration found in the adult mammalian retina following optic nerve injury has led to the study of cell and tissue engineered cell delivery methods. However when designing these delivery devices, it is necessary to orient retinal ganglion cell (RGC) axon growth and cellular organization to mimic that of the nerve fiber layer as well as stimulate dendrite growth and synapse formation with the cell binding partners in the host retina. Biodegradable scaffolds were produced through electrospinning medical grade PLA using a radial collector which orients fiber formation from the outer edge to a central point designed to mimic the nerve fiber layer of the retina, leading to 81% of seeded RGCs to extend their axon radially. RGC-seeded scaffolds were then cultured in a 3D model with amacrine cells or transplanted to explanted rat retinas. Following co-

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culture and transplantation models, samples formed synaptic connections to amacrine cells in in vitro models and to explanted rat retinas as indicated by immunostaining with synaptic markers as well as synaptic tracing viruses. 60% of samples were also observed to have RGC axons reach the optic nerve head in transplantation models. Together these results indicate a significant step forward in the transplantation of retinal ganglion cells for diseases of the optic nerve.

24. Darrell Andrews, University College Dublin

Targeting the Polycomb Repressor Complex chromatin remodeling machinery for therapeutic benefit in Diabetic retinopathy

Darrell Andrews,1 Letizia deChiara,1 Giorgio Oliviero,1 Gerard Cagney,1 Colm O’Brien,2 John Crean.1

During the initiation and progression of diabetic retinopathy cells within affected tissues undergo a process of reprogramming, evoking gene expression profiles reminiscent of ontogenesis. In vitro and in vivo studies have identified members of the Transforming Growth Factor-β superfamily as central to these processes. We have previously described SMAD3 and EZH2 as part of a context dependent switch enhancing complex that regulates cell fate during fibrotic processes. Here we describe further characterisation of this interaction and delineate its potential pathogenic significance. Comparative analysis of gene expression data from patients and cell models of diabetic eye disease revealed a subset of genes that are potentially regulated by the interaction between Smad3 and EZH2, including critical regulators of epithelial fate such as E-Cadherin.

Mass spectrometry analysis and endogenous immunoprecipitation in retinal epithelial cells studies suggest that cooperative recruitment of PRC2 regulates gene repression during TGF-β mediated differentiation. Luciferase assays using an E-cadherin promoter construct demonstrated that SMAD3 directly binds and recruits EZH2 to the E-Cadherin promoter causing its down-regulation during EMT. Disruption of this interaction was achieved by viral overexpression of miR302. Overexpression of miR032 protected against loss of E-cadherin expression and resulted in down regulation of SMAD3 and induction of SNAIL and EZH2. Our results suggest that SMAD3 and EZH2 control the repression of E-Cadherin during DR, opening the possibility for therapeutic manipulation of this nexus during the progression of retinal disease. Understanding the processes through which dynamic epigenetic silencing is controlled in adults cells will allow us to address the epigenetic state of acquired disease and whether original states, regenerative in nature, can be restored with therapy.

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25. Ana Ruiz-Lopez, University College Cork

Neurotrophic Factor Profile in Retinal Cells and Explants Following Stress

Ana Ruiz-Lopez, Ashleigh M. Byrne, Sarah L. Roche, Alice C. Wyse Jackson and Thomas G. Cotter1*

1* Cell Development and Disease Laboratory, Biochemistry Department, Biosciences Institute, University College Cork, Cork, Ireland.

Purpose: Retinitis pigmentosa (RP) is a retinal neurodegenerative disease caused by the progressive death of photoreceptor cells with 1/4,000 prevalence worldwide. However, the mechanism that leads to blindness is still unknown. Neurotrophic factors are known to help cell survive during the cellular stress caused by neurodegenerative diseases. The objective of the present study was to investigate which neurotrophic factors are up-regulated following cellular stress in the 661w photoreceptor cell line and in retinal explants.

Methods: The 661W photoreceptor cell line and retinal explants from P30 wild type (wt) C57BL/6 mice were used in the experiments performed. Stress was either serum deprivation or chemical in nature for the time indicated. Changes in neurotrophic factor expression were detected by rtPCR and western blotting.

Results: The expression profile of up to 6 neurotrophic factors including NGF, bFGF and EGF was examined in both the cell line and retinal explants. Explants exhibited a higher level of neurotrophic factor expression that probably reflects the stress of the explanting process itself. Following the application of external stress such as serum deprivation or treatment with the cell stressing agent SNP significant change were seen in both 661w cells and explants.

Conclusions: Retinal cells have the ability to increase their production of specific neurotropic factors following stress and understanding how this contributes to cell survival may be pertinent to the use of neuroprotective strategies for the treatment of retinal degeneration. We are grateful to Fighting Blindness Ireland and Science Foundation Ireland for supporting this work.

26. Ashleigh Byrne, Biosciences Institute, University College Cork

The Synthetic Progestin Norgestrel acts to Increase LIF Levels in the rd10 Mouse Model of Retinitis Pigmentosa

Ashleigh Byrne, Tom Cotter

Purpose: Retinal degenerative conditions affect thousands of people worldwide. Retinitis pigmentosa (RP) is among the most common, but it is currently incurable. It is characterised by the progressive death of photoreceptor cells, eventually leading to blindness. Neurotrophic factors play an important role in such retinopathies, and much research has been carried out on their use as treatments. Our group previously

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demonstrated the ability of the synthetic progestin Norgestrel to rescue photoreceptors from cell death, the mechanism of which is believed to include upregulation of the neurotrophic factor bFGF. The objective of the present study was to investigate whether the protection provided by Norgestrel is likely to be mediated by any other neurotrophins.

Methods: 661W photoreceptor cells and retinal explants from P30-P40 wild type (wt) C57BL/6 mice were treated with Norgestrel over time. Homozygous rd10/rd10 mice which harbour a mutation in the pde6b gene and thus mimic the human form of RP were fed either a control or a norgestrel containing diet. Subsequently, rtPCR, western blotting or immunofluorescence staining were used to detect changes in neurotrophic factor expression in response to Norgestrel.

Results: We found leukaemia inhibitory factor (LIF), a potent neuroprotective cytokine, to be upregulated in response to Norgestrel. Both the 661W cells and retinal explants displayed significant increases in LIF mRNA with concomitant increases at the protein level. Rd10 mice kept on the Norgestrel diet also exhibited increases in LIF in various layers of the retina, and preservation of the photoreceptor layer in P20 rd10 mice.Conclusions: Norgestrel increased levels of LIF in all models studied. This increase was concurrent with rescue of the photoreceptor cell layer in rd10 mice undergoing retinal degeneration. These results highlight the ability of Norgestrel to induce pro-survival molecules in the compromised retina, underlining its potential as a viable drug for the treatment for RP.

27. Anna-Sophia Kiang, Trinity College Dublin

Enhanced Drug Delivery to Rodent Retinas Following Inner Blood-Retina Barrier Modulation.

Kiang A-S, Campbell M, Keaney J, Humphries MM, Farrar GJ, Kenna PF and Humphries P.

Author AffliationsOcular Genetics Unit, Smurfit Institute of Genetics, Trinity College Dublin, Ireland.

Purpose: To enhance retinal delivery of hsp90 inhibitor 17-DMAG and to assess therapeutic efficacy in two rodent models of RP, study mechanism of action of 17-DMAG and quantify drug uptake by mass spectrometry.

Methods: Doxycycline-inducible iBRB modulation; ERG analysis; LC/MS/MS; cell culture; RT-PCR; immunoblotting; histology.

Results: Modulation of iBRB enhances delivery of 17-DMAG to retina as evidenced by LC/MS/MS quantitation. Retinal degeneration retarded in eyes in which drug delivery was enhanced compared to controls. Ongoing research indicates that the mode of action involves components of the unfolded protein response.

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Conclusion: Transient inducible modulation of the iBRB is a promising method for enhancing delivery of therapeutics to retina. Hsp90 inhibitors are just one class of many compounds which could be of therapeutic benefit in ocular disorders.

28. Kepil Dev, National University of Ireland, Galway

Generation of Induced Pluripotent Stem Cells from Patients Harboring a RPE65 Mutation using a Mon-integrative Reprogramming Method

Kapil Dev#, Eva Carvalho#, Yicheng Deng, Cormac Murphy, Linda Howard, Sanbing Shen

Regenerative Medicine Institute, Bioscience Research Building, National University of Ireland (NUI) Galway, Ireland. #These authors contributed equally to this work.

Retinitis pigmentosa is a devastating retinal degenerative disease with progressive death of rod photoreceptors as well as cones at later stage. It impairs vision at a rate of 1/3200 and affects approximately 1.5 million worldwide. There is no effective treatment available to restore the vision. Retinitis pigmentosa is an inherited retinal degeneration with >60 causative genes identified. There is a large family suffering retinitis pigmentosa in Ireland, with 2/3 of the family members affected. Whole exome sequencing has identified a unique dominant negative mutation of RPE65 c.1430G4A, which results in a change of amino acid 477 from Asp to Gly. This Irish family therefore offers a unique opportunity to investigate novel disease mechanisms of retinitis pigmentosa. The lack of human disease models has hampered our understanding of the disease and the development of therapeutic treatment. The induced pluripotent stem cell (iPSC) technology developed by Yamanaka, which can reprogram somatic cells into embryonic stem cell (ESC) -like cells that can be differentiated into most cell types in the body including photoreceptors, provides an opportunity for visualizing disease progression in vitro, for generating human disease models to enable drug discovery, and for developing photoreceptor replacement therapy using patient’s own somatic tissues. Here we report that, toward this goal, we have cultured and banked dermal fibroblasts from three RPE65 c.1430G4A patients and derived iPSCs from patients’ fibroblasts using a non-integrative method. The iPSCs from three RPE65 patients are preliminarily characterized for the expression of pluripotency markers including Alkaline Phosphatase, OCT4, SOX2, NANOG, TRA-1-60, TRA-1-81 and SSEA4. These RPE65 iPSC lines were found to be positive for the pluripotent stem cell markers. We now have human RPE65 c.1430G4A iPSC lines to investigate disease pathology and molecular mechanisms during photoreceptor differentiation.

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Retina 2015 Organising Committee

1. Ms Avril Daly CEO, Fighting Blindness

2. Dr Maria Meehan Research Manager, Fighting Blindness

3. Caitríona Dunne Communications and Advocacy Executive,

Fighting Blindness

4. Siobhán Collins Assistant to CEO, Fighting Blindness

5. Mr David Keegan Consultant Ophthalmic Surgeon, Institute of

Ophthalmology, Mater Misericordiae Hospital

6. Ms Giuliana Silvestri Consultant Ophthalmic Surgeon, Clinical Director for

Ophthalmology Services, Royal Hospitals, Belfast

7. Prof Alan Stitt Centre Director, School of Medicine, Dentistry and

Biomedical Science, Queen’s University Belfast

8. Prof Tom Cotter Professor of Biochemistry & Cell Biology, BioSciences

Institute, University College Cork

9. Dr Paul Kenna Clinical Ophthalmologist, Royal Victoria Eye and. Ear

Hospital and Senior Clinical Research Fellow, Ocular Genetics Unit at Trinity College Dublin

10. Dr Breandán Kennedy Principal Investigator, School of Biomolecular and

Biomedical Sciences, Conway Institute, University College Dublin

Fighting Blindness were a founding charity of the Medical Research Charities Group (MRCG) and we participate in an innovative joint funding scheme between the MRCG and the Health Research Board. The scheme allows members of the MRCG to support research of particular interest to specific patient populations.

Since 2006, Fighting Blindness has been successful in every call of this scheme which provides funding for clearly defined research projects in disease areas of strategic relevance to the charity.

The call for the 2016 funding scheme is now open. Short one page letters of intent should be forwarded to maria.meehan@fightingblindness.ie by Monday, November 30. Full applications will be subject to rigorous peer review with projects expected to begin by September 2016.

Funding Scheme Now OpenMRCG/HRB 2016

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