Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration
| Autor: | Takuji Shirasawa, Kouhei Hashizume, Kazuo Tsubota, Satoshi Uchiyama, Setsuko Noda, Yutaka Mizushima, Mineko Yamaguchi, Yutaka Imamura, Takahiko Shimizu, Kei Shinoda |
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| Rok vydání: | 2006 |
| Předmět: |
Retinal degeneration
Pathology medicine.medical_specialty genetic structures Light Mice Transgenic Drusen Neovascularization Macular Degeneration Mice chemistry.chemical_compound Superoxide Dismutase-1 medicine Animals Pigment Epithelium of Eye Optic Disk Drusen beta Catenin Multidisciplinary Retinal pigment epithelium Neovascularization Pathologic Superoxide Dismutase business.industry Retinal Choroid Diseases Anatomy Biological Sciences Macular degeneration medicine.disease eye diseases Mice Inbred C57BL Disease Models Animal Oxidative Stress Choroidal neovascularization medicine.anatomical_structure chemistry sense organs medicine.symptom business |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:11282-11287 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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