Superoxide dismutase 1 protects retinal cells from oxidative damage
Superoxide dismutase 1 protects retinal cells from oxidative damage
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DOI：
10.1002/jcp.20683
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发表时间：
2006-09-01
影响因子：
5.6
通讯作者：
Campochiaro, Peter A.
中科院分区：
文献类型：
--
作者：
Dong, Aling;Shen, Jikui;Campochiaro, Peter A.
支持内源性氧化损伤防御系统是开发治疗以对抗氧化损伤起作用的神经退行性疾病的良好策略。这种治疗方法开发的第一步是确定防御系统的各种成分在退化细胞中的作用。在这项研究中，我们试图确定超氧化物歧化酶1（SOD 1）在两种氧化损伤诱导的视网膜变性模型中的作用。在一个模型中，百草枯被注射到玻璃体腔中，然后进入视网膜细胞并产生活性氧（ROS），导致进行性视网膜损伤。用连续视网膜电图（ERG）评估视网膜功能表明，sod 1（-/-）小鼠对百草枯的损害作用比sod 1（+/+）小鼠敏感得多，而sod 1（+/-）小鼠表现出中等敏感性。与sodi（+/+）小鼠相比，sod 1（-/-）小鼠表现出更强的百草枯诱导的氧化损伤和细胞凋亡。在第二个模型中，小鼠暴露于高氧数周，sod 1（-/-）小鼠的ERG振幅比sod 1（+/+）小鼠显著降低。在这两种模型中，转基因小鼠携带由P-肌动蛋白启动子驱动的sod 1转基因表现出较少的氧化应激诱导的ERG振幅降低。这些数据表明，SOD 1保护视网膜细胞对百草枯和高氧诱导的氧化损伤，并建议，过表达的SOD 1应被视为一个组成部分的眼部基因治疗，以防止氧化损伤诱导的视网膜变性。
Bolstering the endogenous oxidative damage defense system is a good strategy for development of treatments to combat neurodegenerative diseases in which oxidative damage plays a role. A first step in such treatment development is to determine the role of various components of the defense system in cells that degenerate. In this study, we sought to determine the role of superoxide dismutase 1 (SOD1) in two models of oxidative damage-induced retinal degeneration. In one model, paraquat is injected into the vitreous cavity and then enters retinal cells and generates reactive oxygen species (ROS) that cause progressive retinal damage. Assessment of retinal function with serial electroretinograms (ERGs) showed that sod1(-/-) mice were much more sensitive than sod1(+/+) mice to the damaging effects of paraquat, while sod1(+/-) mice showed intermediate sensitivity. Compared to sodi(+/+) mice, sod1(-/-) mice showed greater paraquat-induced oxidative damage and apoptosis. In the second model, mice were exposed to hyperoxia for several weeks, and sod1(-/-) mice showed significantly greater reductions in ERG amplitudes than sod1(+/+) mice. In both of these models, transgenic mice carrying a sod1 transgene driven by a P-actin promoter showed less oxidative stress-induced reduction in ERG amplitudes. These data demonstrate that SOD1 protects retinal cells against paraquat- and hyperoxia-induced oxidative damage and suggest that overexpression of SOD1 should be considered as one component of ocular gene therapy to prevent oxidative damage-induced retinal degeneration.