Conjunctiva• Thin, semitransparent, vascularized mucous

membrane that covers the posterior surface of the eyelids and anterior surface of sclera

• responsible for the production of mucous• defensive inflammatory reaction• neutralize foreign particles, such as viruses.

conjunctiva

palpebral

marginal

tarsal

orbital

bulbar Scleral

Limbalfornix

Palpebral conjunctiva adherent to the tarsal plate of the lids.

- Marginal – From lid margin to sulucs marginalis. It is a transitional zone between skin and conjunctiva. Here cells change from keratinized str.sq.ep. To nonkeratinized. Lacrimal puncta opens here.

- Tarsal – thin, transparent , higly vascular. Attached to the tarsal plate. It contains tarsal glands - small saccular mucus glands. tarsal conjunctiva is continually covered with tears. “Suptarsal grooves” = anatomical trap for small foreign objects. It is this area, lacrimal puncta open to connect the conjunctival sac with the nose. Nasal tarsal conjunctiva contains Henle's mucus crypts - network of subepithelial grooves.

- Orbital part – between tarsal plate and fornix. Attached to the Muller muscle. Shallow grooves and elevations – Stieda’s plateaux

Bulbar Conjunctiva• Thin, transparent and can be moved easly. Smoother.• Extends from the limbus to the forniceal area. • Seperated from anterior sclera by Tenon’s capsule. • 3 mm ridge of bulbar part around the cornea is called

limbal conjunctiva • 1) Contains stem cells for corneal epithelial prolifatarion, 2) migrate during healing and defect of the cornea. 3) retain thymidine and express unique protein a-enolase.

Forniceal Conjunctiva• Joins palpebral and bulbar conjunctiva• Ducts of the lacrimal glands open in the superior fornix• The superior fornix – largest. pass from the levator

palpebral superioris muscle.• temporal fornix - tendon of the lateral rectus muscle• The inferior fornix is attached to the tendon of the inferior

rectus• fornix medially changed by plica semilunaris and caruncle

Goblet Cells Henle’s Glands Glands of Manz

Releases mucus in the form of packets.Absent in Marginal and Limbal

Tubular strucutes contain Goblet cells.

In the scleral conjunctiva

Dystrois after discharging mucin

Present in the folds of mucous membrane in palp.conj.

Makes ring around the cornea

Glands of Krause Glands of Wolfering

Deep in upper and lower fornices42 in upper. 6-8 lower

Larger than Krause

Between palpebral part of lacrimal gland and tarsal plate

2-5 in the upper lid1-3 in the lower lid

• Lid margins - keratinized nonkeratinized• Upper tarsal portion s- tratified epithelium (3-4 layer)• Corneoscleral junction – stratified epithelium (6-8 layer)• Conjunctival margins – stratified epithelium (8-10 layer)• Fornix – columnar, stratified epithelium (3 layers)• bulbar and tarsal – cuboidal,Stratified squamous (2-3layer)

Epitheliumstratified epithelial layer

substantia propria:Adenoid and Fibrous

Function of Conj. Epith. • Resoprtion. Tears and medication can be absorbed • contribution to the tear film• Production of proteins and cytokines: MUC1 and MUC 5 • Stabilizing and anchoring the tear film by mucin like

proteins

Surface epithelial cellsType I cells – Goblet cells. produce the mucinous layer of the tear film. found throughout the conjunctiva except at the limbus. most frequently found in the fornix. derived from epithelial stem cells.Type II cells - large granules. most common cells in the human conjunctiva. highest amount is found in the tarsal and forniceal conjunctiva. Type III cells – cells with welldeveloped Golgi complex. vacuoles that can reach the epithelial surface. vesicles are released outward for mucinous secretions.Type IV cells – secrets specific proteins for tear film.Type V cells – high content of mitochondria. Thay make energy for resoprtion.

Goblet Cells• Presents in the middle and superficial layer of epithelium and

attached to other epithelial cells by desmosomes. • The inferior conjunctiva contains more goblet cells.15% of epithelial

surface cells. Lower nasal fornix• Goblet cells are the major producers of mucins for the tear film. Thay

may produce up to 2.2 μL of mucus daily. • Corneal debridement causes goblet cell secretion while damage by

releasing neurotransmitters: VIP, serotonin, dopamine. • Contributes local immunity by IgA and lysozyme. • Glycoproteins: sialomucins and sulphomucins. • Wearers of soft contact lenses for many years, have reduced density

of goblet cells, results in Dry eye• Beta-blockers also cause a pronounced reduction of goblet cells.

Non-goblet cell epithelium - Another source of mucus production. Contains: sulfomucin, sialomucin. Apical cells have small vesicles, thay deliver mucins onto the ocular surface.Substantia Propria – connective tissue layer with anti-infectious potential. Mast cells + lymphocytes, plasma cells, neutrophils, IgG, IgA, IgM.It has 2 layers - superficial lymphoid layer (lymohocytes aggrgated by nodules) and a deeper fibrous layer (collagen, elastin, vesslels, nerves)Melanocytes: in limbus, fornix, plica semilunaris, caruncle, perforation of anterior ciliary vessels.

Conjunctival Veins - Major portion: tarsal and bulbar palpebral veins or independently into SOV. Circumcorneal zone of veins 5-6 mm from limbus

Arteries

Peripheral tarsal arcade

Marginal tarsal arcade

anterior ciliary artery

Conjunctival Nerve SupplyFrom the first division of the trigeminal nerve. infratrochlear branch of the nasociliary nerve, the lacrimal nerve, the supratrochlear and supraorbital branches of the frontal nerve, and the infraorbital nerve from the maxillary division of the trigeminal nerve. The limbal area is supplied by branches from the ciliary nerves. The majority of nerve endings in the conjunctiva are free, unmyelinated nerve endings.

Function of the Tear Film• maintaining the health of corneal and conjunctival

epithelia• acting as the first line of defense against microbial

infections• Provide refraction for light• Trasnfers O2 from air to cornea• Keep the cornea surface moist

Between the mucous layer and the corneal and conjunctival epithelia there is a mucin-containing glycocalyx

Conjunctiva Mucous Layer

Main and accessory lacrimal glands Aqueous Layer

Meibomian Gland Lipid Layer

Mucin Layer• mucin, immunoglobulins, urea, salts, glucose, leukocytes,

cellular debris, and enzymes.• Glycoproteins – 50-80% carbohydrate• Abundant aminoacids: serine and threonine• highly hydrophilic• Negatively charged

Secretory mucins

•large gel-forming mucins•small soluble mucins

membrane-associated

Membrane-assosicated mucins• form the glycocalyx, barrier for pathogens• Affect on epithelial activity by facilitating siganl

transduction. • Contains epidermal growth factor (EGF)-like domains

Secreted mucins• move easily over the glycocalyx• act as a “cleaning crew,”

Aqueous Layer• Formed by main and Krause and Wolfering• Contains water, electrolytes, proteins, peptide growth

factors, immunoglobulins, cytokines, vitamins, antimicrobials, and hormones secreted by the lacrimal glands.

• Electrolytes: Na, Ca, K, Mg, P.• Buffers: maintain constant pH.• More than 60 proteins: albumin, Ig, histamine …• Antimicrobial proteins: Lysozyme, lactoferrin, and lipocalin• Contains Peptide Growth Factor, Vitamin A regulate

epithelila proliferation.

Lipid layer• 0.1um thick• Polar lipid phase - phospholipids and glycolipids• nonpolar lipid layer - wax, cholesterol esters, and

triglycerides.• reduce evaporation by 90%• Meibomian Gland regulated by hormons, nerves

LACRIMAL FUNCTIONAL UNIT1. Parasymphatetic Fibers (acetylcholine and

vasoactive intestinal peptide [VIP])2. sympathetic nerves (neuropeptide Y and

norepinephrine)3. sensory fibers trigeminal nerve (substance P and

calcitonin gene-related peptide)Reflex Secretion

Result from irritation of the eye by foreign body.Sympathetic and parasympathetic nerves that innervate the ocular surface epithelia stimulate tear production.

GOBLET CELL SECRETION

CONJUNCTIVAL INFLAMMATIONFeatures are:hyperemia - redness of injection. Neurogenic or vasoactive substances produce blood vessel dilatation.edema (chemosis) – from endothelial injury of realese vasoactive substances, like histamine, serotonine. Endothelial cells contract.Papillae – small (max. 1mm), hyperemic projections. Contains central fibrovascular core of vessels. Giant papillae – (more than 1mm) atopic and palpebral vernal keratoconjunctivits. In limb – trantas dots.Follicles: mostly in the fornix (05-1.5mm) oval, eleveated. Avascular lesions. Thay are lymphocytes from substantia propria. Most commonly assosiated with viral or chlamydial infection.

CONJUNCTIVAL INFLAMMATIONMembrane formation – true membrane: fibrin, fibrinous byproducts, leukocytes, necrotic debris. When removed, causes bleeding.. Diphteria cinjunctivits, Neisseria gon., strep. Steven-johnson. Pseudomembrane – similar compostion, less adherent to underlying epithelium. No bleeding. Viral, bacterial, alkali burns.Cinjunctivits may present with cellular exudate. If there is polymorphonuclear leukocytics response, it can be bacterial or fungal, toxic drug reaction or necrosis.Recurrent inf. – reactive and degeneration changes. Epithelium and goblet cells undergo hyperplasia - Pseudoglands of Henle. Ectropion associated with epidermalization of palpebral conjVit A def. dry eye.

CONJUNCTIVAL WOUND HEALINGProliferation of basal layer reestablishes normal thickness of epithelium. 1cm large conjunctival wound reepithelialized within 48-72 hours.1. Clot phase – immediately after injury. Blood vessel

contraction.2. Proliferation phase – fibroblasts, new capillaries,

inflamatory cells migrate into the clot and replicate. After 5 days it forms fibrovascular CT or granulation tissue.

3. Granulation phase – after 10 days.4. Collagen phase – Aggregation of tropocollagen molecules

to form mature collagen.

CONJUNCTIVAL HEALING IN GLAUCOMA FILTERING SURGERYA subconjunctival accumulation of aqueous called - filtering bleb – after successful glaucoma surgery.Aqueous has 2 ways: 1. Reabsoprtion by blood vessels2. Movement through conjunctival epithelium into the tears Failed blebs – scarred to the underlying episclera, heavily vascularized, no microcysts. Drugs inhibiting fibroblast proliferation decease risk of bleb failure. 5-Fluoroucil, mitomycin-C.

CLINICAL EVALUATION OF THE TEAR FILMTEAR SECRETION measurmentSchirmer I – measures reflex tear secretion in response to conjunctival stimulation. Placing a strip of Whatmand #41 paper. Less than 10mm without anesthetic means deficiency, with anesthetic less than 5mm.Schirmer II – measures reflex tear secretion in response to nasal stimulation. Whatman paper is placed in the lower eyelid, followed by stimulation of nasal mucosa with cotton-tripped applicator or smelling amonia. Wetting less than 15mm means deficinecy. Phenol Red Thread Test – pH sensitive dye. Dyed with phenol red is placed in the lower eyelid. Less than 6mm means dry eye.Meniscometry - measuring the tear meniscus radius. Videomeniscometer records images of the ocular surface with a digital video recorder and transfers them to a computer - calculate the radius of curvature.

Lipid Layer EvaluationInterferometry – determines lipid layer thickness and fluidity.Studies have shown greater tear film stability with a thicker lipid layerMeibometry - level of meibomian lipids by laser device. __________________________________________________Human precorneal tear film pH measured by microelectrodes. the mean was pH 7.6. Stimulation of tear secretion and blinking led to a decrease in the pH value.

DRY EYE2 types: evaporative and tear defecient – Sjögren and non- Sjögren

Sjögren Syndrome – autoimune exocrinophaty. lymphocytic infiltration result of a functional blockage in the neural pathway caused by inflammation. Inflamation blocks release of neuritransmitters. Women are more likely. One of the causes is androgen deficient. may be primary or secondary. Primary: combination with dry mouth, the presence of autoantibodies. secondary when it occurs in association with other autoimmune connective tissue disorders, rheumatoid arthritis being the most common.

DRY EYENon-Sjögren Syndrome – include primary and secondary lacrimal deficiencies and congenital alacrima. Primary lacrimal deficiency (PLD) Riley-Day syndrome - caused by abnormal parasympathetic innervation of the lacrimal glandMedications: diuretics, antimuscarinic effect, antihistamines, antihypertensives, and antipsychotic drugs.Cicatrizing diseases: trachoma, ocular cicatricial pemphigoid, erythema multiforme and Stevens-Johnson symdrome, and chemical and thermal burns

Zura Glonti2017