Neuroprotective role of retinal SIRT3 against acute photo-stress

Abstract

Author Summary Sirtuins are nicotinamide adenine dinucleotide-dependent protein deacetylases. Among seven sirtuins, SIRT3 is a key regulator of mitochondrial function. However, functions of SIRT3 in the retina are largely unknown. In this study, we investigated the role of retinal SIRT3 in a mouse model of light-induced retinal degeneration, found that SIRT3 has neuroprotective role in the retina. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress, and decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These results suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.