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Alexander Hua, Tytteli Turunen, Gianna C Teague, Marie Shantos, Kameran Lashkari; Light-Induced Retinal Damage in Rodents as an Interventional Model for Neurotrophic Treatment for Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2445.
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© ARVO (1962-2015); The Authors (2016-present)
In geographic atrophy (GA) associated with end-stage dry AMD, visual function impairment is the consequence of the loss of photoreceptor (PR) and RPE cells. Advances in understanding GA has been hampered by lack of a reliable animal model, resulting in failure of several clinical trials. In this study we present a photic model of outer retinal injury, which recapitulates key aspects of clinical GA and can be manipulated by pharmacological intervention.
Brown Norway rats were exposed to white/blue light using a Micron III fundus camera directed to specific locations in the retina to recapitulate GA lesions, and followed between 0-30 days. Eyes were treated with topical 1% or intravitreal (IVT) brimonidine (1-10 ug/5ul) or vehicle. Geographic lesions were studied by SD-OCT, fundus autofluorescence, color fundus photography and fluorescein angiography. GA lesions images were measured on NIH ImageJ. Eyes were dissected and subjected to immunohistochemistry (IHC) for expression of markers for photoreceptors and microglial.
Directed light damage produced areas of outer retinal/RPE atrophy by 1 month capturing the pathology associated with clinical GA. Atrophic lesions were observed in color fundus photography and autofluorescence. IHC of photic eyes showed aberrant migration of microglia towards site of outer retinal injury. These areas showed RPE loss and photoreceptor cell death. Treatment with brimonidine attenuated lesions size and loss of outer nuclear layer and choroidal thinning.
Our study provides evidence for a photic model of retinal injury in a rat eye and as well as a measurable target for drug treatment for clinical GA. This model can be applied to identify and study novel therapeutic targets and candidate drugs.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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