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Emily Brown, John D Ash, Alfred S Lewin; Deletion of Mitochondrial Antioxidant Enzyme Sod2 Induces Light-Dependent Retinal Degeneration with Aging. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2294. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Conditional deletion of the gene encoding the mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2) was induced in the retinal pigment epithelium (RPE) of albino BALB/c J mice to determine whether elevated mitochondrial oxidative stress causes age-related retinal degeneration and whether normal or dim lighting conditions affect the rate of degeneration.
VMD2Cre;SOD2ff BALB/c J mice were housed in <150 lux red light from birth until wean. Upon wean, mice were either housed in 12-hour dark, 12- hour 200 lux white lighting (normal light), or 12-hour dark, 12-hour <10 lux red lighting (dim light). Electroretinography (ERG) was performed to assess retinal function and spectral-domain optical coherence tomography (SD-OCT) was utilized to examine retinal morphology and outer nuclear layer (ONL) thickness in vivo with aging. IHC was used to examine protein expression; Quantitative RT-PCR was used to measure gene expression.
SOD2 knockout (KO) mice housed in 12-hour 200 lux white lighting had decreased retinal function compared to wild type (WT) littermates as early as 1 month of age. Retinal function continued to decrease with aging in SOD2 KO mice housed in 200 lux lighting, with a statistically significant reduction in the c-wave by 5 months of age (2-way ANOVA, p<0.01,), with no significant differences in the a-wave, b-wave or ONL thickness. Interestingly, there were no differences in retinal function between WT and KO mice housed in dim lighting.
Under normal lighting conditions (~200 lux), but not in dim light, the absence of SOD2 in the RPE resulted in elevated levels of oxidative stress in the RPE and age-related RPE degeneration, suggesting that deletion of SOD2 does not cause oxidative stress and RPE degeneration in the absence of additional stress. These results demonstrate that mild light stimulation, found in a normal animal housing setting, induces biochemical changes in RPE that promote oxidative stress that is normally managed by SOD2. Future studies will aim to determine the mitochondrial mechanism of light-dependent degeneration in the RPE, and how this mechanism plays a role in age-related macular degeneration.
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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