Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration

Yutaka Imamura, Setsuko Noda, Kouhei Hashizume, Kei Shinoda, Mineko Yamaguchi, Satoshi Uchiyama, Takahiko Shimizu, Yutaka Mizushima, Takuji Shirasawa, Kazuo Tsubota

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1-/- mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1-/- mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1 -/- mice showed oxidative damage, and their β-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1-/- mouse is a valuable animal model to study human age-related macular degeneration.

Original languageEnglish
Pages (from-to)11282-11287
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number30
DOIs
Publication statusPublished - 2006 Jul 25

Fingerprint

Choroidal Neovascularization
Retinal Pigment Epithelium
Macular Degeneration
Oxidative Stress
Catenins
Retinal Degeneration
Retinal Pigments
Neurodegenerative Diseases
Free Radicals
Animal Models
Epithelial Cells
Light
Proteins

Keywords

  • Animal model
  • Superoxide dismutase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice : A model of age-related macular degeneration. / Imamura, Yutaka; Noda, Setsuko; Hashizume, Kouhei; Shinoda, Kei; Yamaguchi, Mineko; Uchiyama, Satoshi; Shimizu, Takahiko; Mizushima, Yutaka; Shirasawa, Takuji; Tsubota, Kazuo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 30, 25.07.2006, p. 11282-11287.

Research output: Contribution to journalArticle

Imamura, Yutaka ; Noda, Setsuko ; Hashizume, Kouhei ; Shinoda, Kei ; Yamaguchi, Mineko ; Uchiyama, Satoshi ; Shimizu, Takahiko ; Mizushima, Yutaka ; Shirasawa, Takuji ; Tsubota, Kazuo. / Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice : A model of age-related macular degeneration. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 30. pp. 11282-11287.
@article{b3dff74871bb406690d37a3281f712bb,
title = "Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration",
abstract = "Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1-/- mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1-/- mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1 -/- mice showed oxidative damage, and their β-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1-/- mouse is a valuable animal model to study human age-related macular degeneration.",
keywords = "Animal model, Superoxide dismutase",
author = "Yutaka Imamura and Setsuko Noda and Kouhei Hashizume and Kei Shinoda and Mineko Yamaguchi and Satoshi Uchiyama and Takahiko Shimizu and Yutaka Mizushima and Takuji Shirasawa and Kazuo Tsubota",
year = "2006",
month = "7",
day = "25",
doi = "10.1073/pnas.0602131103",
language = "English",
volume = "103",
pages = "11282--11287",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "30",

}

TY - JOUR

T1 - Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice

T2 - A model of age-related macular degeneration

AU - Imamura, Yutaka

AU - Noda, Setsuko

AU - Hashizume, Kouhei

AU - Shinoda, Kei

AU - Yamaguchi, Mineko

AU - Uchiyama, Satoshi

AU - Shimizu, Takahiko

AU - Mizushima, Yutaka

AU - Shirasawa, Takuji

AU - Tsubota, Kazuo

PY - 2006/7/25

Y1 - 2006/7/25

N2 - Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1-/- mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1-/- mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1 -/- mice showed oxidative damage, and their β-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1-/- mouse is a valuable animal model to study human age-related macular degeneration.

AB - Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1-/- mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1-/- mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1 -/- mice showed oxidative damage, and their β-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1-/- mouse is a valuable animal model to study human age-related macular degeneration.

KW - Animal model

KW - Superoxide dismutase

UR - http://www.scopus.com/inward/record.url?scp=33746628449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746628449&partnerID=8YFLogxK

U2 - 10.1073/pnas.0602131103

DO - 10.1073/pnas.0602131103

M3 - Article

C2 - 16844785

AN - SCOPUS:33746628449

VL - 103

SP - 11282

EP - 11287

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 30

ER -