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Ramesh Periasamy, Wei Zhang, Hemant Khanna, Michael Volkert; OXR1 (oxidation resistance gene 1) Reduces Oxidative Stress and Prolongs Photoreceptor Survival in Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3386. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress contributes to the degeneration of rod and cone photoreceptors in retinal degenerative diseases. More importantly, oxidative stress mediates secondary cone death in retinitis pigmentosa due to mutations in rod-specific genes. Studies have shown that oxidation resistance gene 1 (OXR1) is vital for protecting neurons against oxidative stress. Therefore, we tested if over-expression of OXR1 can prevent or delay the onset of retinal degeneration and blindness in multiple retinal degenerative disease models.
We generated 661W mouse cone photoreceptor cell lines stably overexpressing OXR1. Oxidative stress was induced by exposing the cells to different concentrations of H2O2 (oxidative stress inducer). The resultant increase in cellular oxidative stress resistance was measured by quantifying cell viability using propidium iodide staining. To test the efficacy of our approach in the retina, we delivered adeno-associated viral (AAV) vectors carrying the OXR1 cDNA into the retina by subretinal injection at different disease stages in two mouse models of photoreceptor degeneration. The effect of OXR1 expression was assessed by electroretinography (ERG) to test photoreceptor function and by morphological and cell biological analyses of the retina.
We found that OXR1 expressing 661W cells showed increased viability to H2O2 exposure in a concentration dependent manner. Moreover, AAV-mediated subretinal delivery of OXR1 resulted in significantly improved rod and cone function in the treated retinas of retinal degeneration mice.
OXR1 overexpression is an excellent candidate to prolong photoreceptor survival that can be used in a gene-independent manner in a range of retinal degenerative diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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