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Imran Ahmed Bhutto, Siva Pramodh Kambhampati, D Scott McLeod, Malia Edwards, Gerard A Lutty; A Rat Model of RPE Atrophy Resembling Human Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2289.
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© ARVO (1962-2015); The Authors (2016-present)
Geographic atrophy (GA) is considered the late stage of the dry form of age-related macular degeneration (AMD). While dietary supplements have been shown to reduce the risk of progression in some subcategories of the disease, there is currently no proven drug treatment for dry AMD. The lack of animal models that faithfully mimic all features of the human disease have hampered treatment efforts. In this study, we present a rat model of GA using subretinal injection of sodium iodate (NaIO3).
Athymic nude rats were given bilateral subretinal injections of NaIO3 (5 μg/μl) solution using a pico-injector. Fundus photographs (Micron 3 imaging) and spectral-domain OCT (Heidelberg Engineering Inc.) were collected at post-injection day 1 and 3 as well as 1, 2, 4 and 6 weeks, at which time rats were euthanized and eyes were enucleated. Gross images were taken before isolating retina and choroid. Eyes were either cryopreserved for cross section analysis or dissected to analyze the retina and choroid as flatmounts. Immunohistochemistry (IHC) was used to label retinas for vimentin (Müller cells) and peanut agglutin lectin (PNA). Choroids were immunolabeled with an antibody to RPE65 and GS-IB4 isolectin to label blood vessels. Tissues were assessed on a Zeiss 510 confocal microscope.
Fundus photos, SD-OCT and IHC revealed circumscribed and well-demarcated RPE/photoreceptor/CC lesions in rats treated with subretinal NaIO3. At post-injection day 1, swollen RPE and some photoreceptor loss with activation of Müller cells were clearly visible in the injected area. By day 3, patchy necrotic loss of RPE and majority of the photoreceptors were degenerated in the bleb area and glia had begun entering the subretinal space. RPE and photoreceptors were completely degenerated in the bleb region by day 7. A large subretinal glial membrane occupied the area of photoreceptor and RPE loss. At week 4, in the bleb area lacking RPE underneath CC had begun to attenuate. By week 6, retinal and CC degeneration resembling GA were present in all NaIO3 injected rats.
Using sodium iodate, we have created a reproducible rat model that mimics many aspects of GA including photoreceptor cell loss, RPE atrophy and CC degeneration. Such models are crucial for developing and testing drug treatments and therapeutic interventions such as autologous or stem cell derived treatments for GA.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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