CYCLOPS

Beagle model of primary open angle glaucoma:genetic insight

The only natural animal model of primary open angleglaucoma (POAG) is a colony of Beagle dogs. VanderbiltUniversity researchers have identified a gene (ADMTS10)expressed in these animals’ trabecular meshwork. Thesame gene is found in a comparable section of human chro-mosome 19 that has been previously linked to the regula-tion of intraocular pressure.1 The researchers still have todetermine how the gene is involved in increasing resistanceto aqueous outflow, but they believe the information willlead to a promising target for therapy.

Dry age-related macular degeneration: mechanismproducing geographic atrophy identified

Retinal pigment epithelial cells (RPE) die in geographicatrophy because a microRNA enzyme (DICER1) is re-duced in the RPE of humans with the dry form of AMD.2

The reduction of DICER1 leads to an accumulation of atoxic type of RNA called Alu RNA. Researchers found thatusing mouse models without DICER1, the buildup of AluRNA led to the death of the retina. They were also able toprevent geographic atrophy by using a drug that degraded theAlu RNA. The primary authors are preparing to start clinicaltrials that will test the efficacy of increasing DICER1 and/orreducing the Alu RNA in treating dry AMD.

Inhibiting retinal angiogenesisA mouse model of a type of neovascular AMD was stud-

ied to assess the role of the protein APE1/Ref-1 in thedevelopment of angiogenesis.3 A small molecule inhibitorof APE1/Ref-1, APX3330, was shown, in vivo and in vitro,to block retinal angiogenesis. It is suggested that targetingAPE1/Ref-1 may offer treatment options not only for neo-vascular AMD but other neovascular diseases as well.

Mouse model of retinitis pigmentosa (RP) mayexplain photopsias in RP patients

Many RP patients report seeing flashes of light (photop-sias) that are unlikely to have their origin from the degen-erated photoreceptors. Working with the rd1 mouse, amodel of human RP, German scientists were able to recordwaves of electrical activity that suggest an origin for thephotopsias.4 They used a dense array of thousands of mi-croelectrodes and recorded from the still-functional gan-glion cells, finding rhythmic but asynchronous activity.They speculate that this knowledge of abnormal electricalactivity could guide treatment strategies for RP.

Aging vision: sensing of self-motion impairedWhen we move forward there is a radial optic flow that

gives us information about our heading and our speed. It

turns out that, as we age, the visual system’s ability to usethis information declines, impairing our ability to navigatethrough our environment.5 The Rochester, N.Y. investi-gators also studied this decline in Alzheimer’s disease pa-tients and found it was impaired in a different way. Theresults have implications for the prevention of falls, andother motility problems, in the elderly.

Adult cortical plasticity: evidence from thecongenitally blind

Three articles appeared recently that show the visualcortex and other pathways, thought to be exclusively forvision, can process tactile and linguistic information inadult congenitally blind people.6-8 This is further evidencethat the adult brain can change, a finding that has beenfeatured in a number of articles described in this columnover the years.

Retinal ganglion cells: development, function anddisease

Papers from the 13th Annual Vision Research Confer-ence, held in Florida in 2010, have just been published ina special issue of Vision Research.9 Speakers reviewed thelatest developments in pathogenesis/optic nerve damage,ganglion cell development, and photosensitive ganglioncells. It is a useful compendium of up-to-date findings onthese topics.

REFERENCES

1. Kuchtey J, Olson LM, Rinkoski T, et al. Mapping of the disease locus andidentification of ADAMTS10 as a candidate gene in a canine model ofprimary open angle glaucoma. PLoS Genet. 2011;7:e1001306.

2. Kaneko H, Dridi S, Tarallo V, et al. DICER1 deficit induces Alu RNAtoxicity in age-related macular degeneration. Nature. 2011;471:325-30.

3. Jiang A, Gao H, Kelley MR, Qiao X. Inhibition of APE1/Ref-1 redoxactivity with APX3330 blocks retinal angiogenesis in vitro and in vivo.Vision Res. 2011;51:93-100.

4. Menzler J, Zeck G. Network oscillations in rod-degenerated mouse reti-nas. J Neurosci. 2011;31:2280-91.

5. Kavcic V, Vaughn W, Duffy CJ. Distinct visual motion processing im-pairments in aging and Alzheimer’s disease. Vision Res. 2011;51:386-95.

6. Bedny M, Pascual-Leone A, Dodell-Feder D, Fedorenko E, Saxe R. Lan-guage processing in the occipital cortex of congenitally blind adults. ProcNatl Acad Sci U S A. 2011;108:4429-34.

7. Trampel R, Ott DV, Turner R. Do the congenitally blind have a Stria ofGennari? First intracortical insights in vivo. Cereb Cortex. 2011;Feb 10[Epub ahead of print].

8. Reich L, Szwed M, Cohen L, Amedi A. A ventral visual stream readingcenter independent of visual experience. Curr Biol. 2011;21:363-8.

9. Wensel T, Baehr W. Ganglion cells (Special Issue). Vision Res. 2011;51:entire issue.

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 mjs@yorku.ca.

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