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CYCLOPS
Regenerating the optic nerveTwo recent papers describe the regeneration of damaged
ganglion cell axons in mouse models. Both exploited thefact that cyclic adenosine monophosphate (cAMP) is crit-ical for both neuronal survival and axon growth. The first,from Bascom Palmer Eye Institute, showed that solubleadenylyl cyclase activity plays a crucial role in the cAMPregenerative process.1 The second, from Boston Children’sHospital, increased cAMP along with a growth-promotingcompound called oncomodulin. These interventions notonly regenerated optic nerve, but they also restored somevisual functions.2 The Boston group traced fibre growthfrom the optic nerve to the thalamus and midbrain, andthese connections allowed (1) circadian cycles to be re-stored, (2) a degree of depth perception to be observed, and(3) an optokinetic head response to moving stripes to bedetected.
Growing an eyeJapanese researchers had previously shown that mouse
embryonic stem cells could be coaxed into growing an eyecup that had the correct 3-dimensional shape and layeringof tissues. They have now extended this finding, this timeusing human embryonic stem cells, and have grown an eyecup that is twice the diameter and 10 times the volume ofthe mouse cup.3 The technique could someday allow inte-grated photoreceptor tissue to be transplanted into thesightless eyes of blind humans.
Growing new rodsUK scientists were able to transplant photoreceptor pre-
cursors into a mouse model that lacks rod function.4 Neu-ral connections were made to bipolar and horizontal cellswhich were then shown to have functional behavioral cor-relates. Under scotopic levels of illumination they observed(1) optokinetic head tracking and (2) successful escapefrom a water maze in the mice with transplanted rods.Photoreceptor transplantation may yet be able to restorevision in patients with retinal degeneration.
Restoring binocular vision in amblyopic miceFrench scientists have uncovered a possible therapeutic
tool for restoring cortical plasticity in the adult brain.5
Using a mouse model, they showed how a homeoprotein(Otx2) could alter critical period opening and closing. Theprotein was injected into V1 and plasticity recovery wasassessed using single-unit electrophysiology as well asevoked potentials.
G protein signaling and scotopic vision in the mouseTwo papers from the same lab in Florida’s Scripps Re-
search Institute have uncovered roles for proteins that are
C
important for scotopic vision. The protein family is Regu-lator of G Protein Signaling (RGS). The first study showedthat two members of this family, RGS7 and RGS11, allowthe transmission of neural signals from rod photoreceptorsthrough the bipolar cells to the ganglion cells.6 The secondstudy identified previously unknown G protein-coupledreceptors (GPCRs) that interact with the RGS proteins.7
Mutations in the genes that encode these proteins may beresponsible for congenital stationary night blindness.
Hemianopic field loss: auditory stimulationprovides benefits
Ten patients with homonymous hemifield loss fromstroke were enrolled in a German study that presentedfiltered noise from loudspeakers located in the blind hemi-field.8 They listened passively to this noise for a one-hourperiod, and their ability to detect a light flashed in theblind or sighted field was tested afterwards. The passiveauditory exposure improved their ability to detect lightflashes in the blind field immediately after stimulation butthis capacity dissipated after 1.5 hours. The authors inter-pret their findings as indicating connections between sen-sory systems, e.g., as in the superior colliculus where audi-tory and visual information is processed simultaneously.Cross-modal stimulation may become another rehabilita-tion technique for other forms of visual rehabilitation.
REFERENCES
1. Corredor RG, Trakhtenberg EF, Pita-Thomas W, et al. Soluble adenylylcyclase activity is necessary for retinal ganglion cell survival and axongrowth. J Neurosci. 2012;32:7734-44.
2. de Lima S, Koriyama Y, Kurimoto T, et al. Full-length axon regenerationin the adult mouse optic nerve and partial recovery of simple visual be-haviors. Proc Natl Acad Sci U S A. 2012;109:9149-54.
3. Nakano T, Ando S, Takata N, et al. Self-formation of optic cups andstorable stratified neural retina from human ESCs. Cell Stem Cell. 2012;10:771-85.
4. Pearson RA, Barber AC, Rizzi M, et al. Restoration of vision after trans-plantation of photoreceptors. Nature. 2012 May 3;485:99-103.
5. Beurdeley M, Spatazza J, Lee HH, et al. Otx2 binding to perineuronalnets persistently regulates plasticity in the mature visual cortex. J Neurosci.2012;32:9429-37.
6. Cao Y, Pahlberg J, Sarria I, et al. Regulators of G protein signaling RGS7and RGS11 determine the onset of the light response in ON bipolarneurons. Proc Natl Acad Sci U S A. 2012;109:7905-10.
7. Orlandi C, Posokhova E, Masuho I, et al. GPR158/179 regulate G pro-tein signaling by controlling localization and activity of the RGS7 com-plexes. J Cell Biol. 2012;197:711-9.
8. Lewald J, Tegenthoff M, Peters S, Hausmann M. Passive auditory stim-ulation improves vision in hemianopia. PLoS One. 2012;7:e31603.
Cyclops provides a singular view of the basic science literature onvision and is a sampling of what’s new and interesting. The au-thor, Martin J. Steinbach, PhD, welcomes your feedback and
suggestions, which can be sent to [email protected].AN J OPHTHALMOL—VOL. 47, NO. 5, OCTOBER 2012 397
