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
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U2 - 10.1073/pnas.0602131103
DO - 10.1073/pnas.0602131103
M3 - Article
C2 - 16844785
AN - SCOPUS:33746628449
SN - 0027-8424
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
IS - 30
ER -
