Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration
Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration
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DOI：
10.1073/pnas.0602131103
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发表时间：
2006-07-25
影响因子：
11.1
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Imamura, Yutaka;Noda, Setsuko;Tsubota, Kazuo
氧化应激长期以来一直与神经退行性疾病的发病机制有关;然而，它是否是退行性过程的原因或仅仅是结果仍然未知。我们发现，铜，锌-超氧化物歧化酶（SOD 1）缺乏的小鼠具有典型的人类年龄相关性黄斑变性的特征。对不同年龄的衰老Sod 1（-/-）小鼠的研究表明，年龄较大的动物有玻璃疣、增厚的布鲁赫膜和脉络膜新生血管。玻璃疣的数量随着年龄的增长而增加，年轻的Sod 1（-/-）小鼠暴露于过量的光诱导玻璃疣。Sod 1（-/-）小鼠的视网膜色素上皮细胞显示氧化损伤，其β-连环蛋白介导的细胞完整性被破坏，表明氧化应激可能影响视网膜色素上皮屏障完整性所必需的连接蛋白。这些观察结果有力地表明，氧化应激可能在年龄相关的视网膜变性中起着致病作用，我们的研究结果为衰老的自由基理论提供了证据。此外，这些结果表明，Sod 1（-/-）小鼠是一个有价值的动物模型，以研究人类年龄相关性黄斑变性。
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.