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Bogale Aredo, Bo Chen, Yuanfei Zhu, Cynthia X Zhao, Yu_Guang He, Rafael Ufret-Vincenty; Mice with a combined deficiency of SOD1, DJ-1 and Parkin develop spontaneous retinal degeneration with aging. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4915. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Chronic oxidative stress is recognized as an important mechanism of disease in aging disorders, including many affecting the retina and the central nervous system. We still do not have a good model system to recapitulate age-related macular degeneration and other retinal disorders in which chronic oxidative stress plays an important role. In this study we hypothesized that mice with a combined deficiency in superoxide dismutase 1 (SOD1), DJ-1 and Parkin (triple knock out, TKO) would have an increased level of chronic oxidative stress in the retina, and that this would have anatomical and functional consequences just with aging.
Age-matched C57BL/6J and SOD1/DJ1/Parkin TKO mice were used at 3-15 months of age. Both male and female mice were used. Eyes were monitored with fundus photography, optical coherence tomography (OCT), and electroretinography (ERG). Eyes were collected from mice of different ages for immunohistochemistry (Iba-1 and MDA), electron microscopy and protein isolation for MDA ELISA.
We show that TKO mice have increased accumulation of fundus spots and retinal microglia by 6 months of age. They also demonstrate qualitative disruptions in outer retinal layers in OCT by 6 months of age, and quantitative changes in retinal thickness by 9 months of age. Furthermore, we found increased accumulation of the oxidative marker malondialdehyde (MDA) in the retina, and increased basal laminal deposits (BLD) and mitochondria in the retinal pigment epithelium (RPE) of aging TKO mice.
The TKO mice demonstrate increased oxidative stress due to aging alone leading to anatomical and functional retinal deficits. We propose that TKO mice can serve as a platform to study retinal diseases that involve chronic oxidative stress, including macular degeneration, retinal detachment, and ischemic retinopathies. In order to model each of these diseases, additional disease-specific catalysts or triggers (e.g. genes, experimental retinal detachment and ischemia) could be superimposed onto the TKO mice. Such studies could provide better insight into disease mechanisms and perhaps lead to new therapeutic approaches.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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