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 beta-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.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, 35-Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. imamura@sc.itc.keio.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.forename: Setsuko
authors.initials: S
authors.lastname: Noda
authors.forename: Kouhei
authors.initials: K
authors.lastname: Hashizume
authors.forename: Kei
authors.initials: K
authors.lastname: Shinoda
authors.forename: Mineko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000818:Animals; D015862:Choroid Diseases / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D008027:Light; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D015594:Optic Disk Drusen / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000606290:SOD1 protein, human; D051176:beta Catenin; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1