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XiangDi Wang, Yunfeng Shi, Monica M Jablonski; Intravitreal NA3 is neuroprotective in the RCS Rat. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4429.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is a debilitating eye disease affecting as many as 25% of individuals past the age of 70 Western cultures. It initially presents as a degenerative disease that does not directly affect photoreceptor cells, but rather it attacks the supportive retinal pigment epithelial (RPE) cells. The purpose of this investigation was to determine if asialo-triantennary (aka NA3) provides neuroprotective support to the retina of the very well characterized Royal College of Surgeons (RCS) rat. In RCS, a mutation in Mertk renders the RPE unable to phagocytize outer segment membranes, thus resulting in layer of outer segment debris that fills the subretinal space and effectively removes the supportive influence of the RPE upon the retina.
P21 RCS rats were dosed intravitreally in both eyes with 5µl of 2.5µM NA3 in PBS either once or twice per week for two weeks. Control groups included PBS injections followed the same time course, and no injections. Electroretinography (ERG), optical coherence tomography (OCT) and visual acuity (VA) data were collected at three time points: baseline before the start of treatment; one week after first injection; and two weeks after first injection. Rats were sacrificed after two weeks of therapy and eyes were enucleated. One eye from each rat was embedded in plastic and thick sections were cut to allow for histological analyses including measurement of retinal layer thickness. The fellow eye is being prepared for GFAP immunochemistry and TUNEL labeling.
The structure and function of the retina was positively affected by NA3. ERG amplitudes (a- and b-waves) and visual acuity measurements were better preserved in NA3-treated eyes compared to PBS-injected or no-injection control rats (p<0.05). The outer nuclear layer thickness was also better preserved in NA3-treated rats. Another physical change we saw was a better organization of photoreceptor outer segments in eyes that were dosed with NA3. Weekly NA3 injections were as or more efficacious than a twice weekly dosing schedule.
Intravitreal NA3 treatment protected photoreceptor structure and function in the RCS rat. It also preserved visual acuity. These data suggest that NA3 may be an effective therapy for atrophic AMD. While we are not claiming that the RCS rat fully mimics atrophic AMD, we are stating that this model can be used to test therapies that support the retina in the absence of a supportive RPE.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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