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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number19
Journalnpj Aging and Mechanisms of Disease
Volume3
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

Reactive Oxygen Species
Retina
Endoplasmic Reticulum Stress
Light
Photoreceptor Cells
Retinal Degeneration
Vertebrate Photoreceptor Cells
Knockout Mice
Oxidative Stress
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Ageing

Cite this

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.

In: npj Aging and Mechanisms of Disease, Vol. 3, No. 1, 19, 01.12.2017.

Research output: Contribution to journalArticle

Ban, Norimitsu ; Ozawa, Yoko ; Osada, Hideto ; Lin, Jonathan B. ; Toda, Eriko ; Watanabe, Mitsuhiro ; Yuki, Kenya ; Kubota, Shunsuke ; Apte, Rajendra S. ; Tsubota, Kazuo. / Neuroprotective role of retinal SIRT3 against acute photo-stress. In: npj Aging and Mechanisms of Disease. 2017 ; Vol. 3, No. 1.
@article{b738ddb17ef1490e9e994a16399e7ce2,
title = "Neuroprotective role of retinal SIRT3 against acute photo-stress",
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.",
author = "Norimitsu Ban and Yoko Ozawa and Hideto Osada and Lin, {Jonathan B.} and Eriko Toda and Mitsuhiro Watanabe and Kenya Yuki and Shunsuke Kubota and Apte, {Rajendra S.} and Kazuo Tsubota",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41514-017-0017-8",
language = "English",
volume = "3",
journal = "npj Aging and Mechanisms of Disease",
issn = "2056-3973",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Neuroprotective role of retinal SIRT3 against acute photo-stress

AU - Ban, Norimitsu

AU - Ozawa, Yoko

AU - Osada, Hideto

AU - Lin, Jonathan B.

AU - Toda, Eriko

AU - Watanabe, Mitsuhiro

AU - Yuki, Kenya

AU - Kubota, Shunsuke

AU - Apte, Rajendra S.

AU - Tsubota, Kazuo

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85050826480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050826480&partnerID=8YFLogxK

U2 - 10.1038/s41514-017-0017-8

DO - 10.1038/s41514-017-0017-8

M3 - Article

VL - 3

JO - npj Aging and Mechanisms of Disease

JF - npj Aging and Mechanisms of Disease

SN - 2056-3973

IS - 1

M1 - 19

ER -