Neuroprotective role of retinal SIRT3 against acute photo-stress

Norimitsu Ban, Yoko Ozawa, Hideto Osada, Jonathan B. Lin, Eriko Toda, Mitsuhiro Watanabe, Kenya Yuki, Shunsuke Kubota, Rajendra S. Apte, Kazuo Tsubota

研究成果: Article査読

13 被引用数 (Scopus)

抄録

SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. 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. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.

本文言語English
論文番号19
ジャーナルnpj Aging and Mechanisms of Disease
3
1
DOI
出版ステータスPublished - 2017 12月 1

ASJC Scopus subject areas

  • 加齢科学
  • 老年医学

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