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Haoyu Mao, Alfred Lewin, Mandy Conners; A new mouse model of dry form AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4604.
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The purpose of this study is to develop a mouse model of geographic atrophy in which mitochondrial oxidative stress is increased by deletion of MnSOD (SOD2), specifically in the retinal pigment epithelium (RPE).
To increase mitochondrial oxidative stress in the RPE, the gene (SOD2) was deleted using the Cre-lox system in which Cre recombinase was expressed only in the RPE following induction with doxycycline. Western blot and Immunohistochemistry was used to confirm RPE reduction in MnSOD, increase in oxidative stress and up-regulation of complement related proteins. Digitial fundus imaging was used to identify pigmentary and vascular abnormalities in the retina. Retinal degeneration in living mice was detected by electrophysiology (ERG) and spectral domain optical coherence tomography (SD-OCT). Light and electron microscopy were used record RPE pathology.
Deletion of SOD2 in the RPE led to evidence of oxidative stress, with increased levels of 8-hydroxy-deoxyguanosine (8-OHdG). Progressive retinal degeneration was observed by ERG and OCT from 1 month to 9 months. Decreased ERG a and b waves response revealed degeneration of the retina. Fundus images and fluorescein angiography showed obvious pigmentary and vascular abnormalities within 6 months. There was no evidence of large drusen-like deposits or of choroidal neovascularization in this model, at least within the first year of observation.
ERG, SD-OCT, fundus images, and fluorescein angiography revealed functional and morphological abnormalities in this mouse model that are analogous some of the findings in patients with geographic atrophy. These findings were confirmed and extended by histology and electron microscopy. This mouse model may therefore be useful for testing treatments to halt the progression of geographic atrophy.
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