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Neuroprotective role of retinal SIRT3 against acute photo-stress.
Ban, Norimitsu; Ozawa, Yoko; Osada, Hideto; Lin, Jonathan B; Toda, Eriko; Watanabe, Mitsuhiro; Yuki, Kenya; Kubota, Shunsuke; Apte, Rajendra S; Tsubota, Kazuo.
Afiliação
  • Ban N; Laboratory of Retinal Cell Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Ozawa Y; Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Osada H; Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, 63110 MO USA.
  • Lin JB; Laboratory of Retinal Cell Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Toda E; Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Watanabe M; Laboratory of Retinal Cell Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Yuki K; Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, 63110 MO USA.
  • Kubota S; Neuroscience Program, Washington University in St. Louis School of Medicine, St. Louis, 63110 MO USA.
  • Apte RS; Laboratory of Retinal Cell Biology, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582 Japan.
  • Tsubota K; Graduate School of Media and Governance, Faculty of Environment and Information Studies, Keio University, 5322 Endo, Fujisawa, Kanagawa 252-0882 Japan.
NPJ Aging Mech Dis ; 3: 19, 2017.
Article em En | MEDLINE | ID: mdl-29214052
ABSTRACT
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.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: NPJ Aging Mech Dis Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: NPJ Aging Mech Dis Ano de publicação: 2017 Tipo de documento: Article