Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice
Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice
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DOI：
10.2353/ajpath.2008.070730
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发表时间：
2008-05-01
影响因子：
6
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Hashizume, Kouhei;Hirasawa, Manabu;Tsubota, Kazuo
超氧化物歧化酶（SOD）家族是一种主要的抗氧化系统，铜锌超氧化物歧化酶（SOD 1）缺乏可导致小鼠出现多种类似加速衰老的表型。本研究的目的是检查Sod 1（-/-）小鼠的感觉视网膜的形态学和生理学。由不同强度的刺激引起的视网膜电图的a-和b-波的振幅在衰老的Sod 1（-/-）小鼠中降低，并且这种振幅的降低随着年龄的增加而更加明显。视网膜形态计量学分析显示，内核细胞层和外核细胞层的细胞核数量减少。电镜观察显示衰老Sod 1（-/-）小鼠的内核细胞和外核细胞层中细胞肿胀和线粒体变性，表明细胞坏死死亡。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记显示，Sod 1（-/-）和野生型小鼠之间的凋亡细胞数量没有显著差异，并且在Sod 1（-/-）小鼠的视网膜中不能检测到活化的caspase-3。除了先前报道的年龄相关性黄斑变性样表型外，Sod 1（-/-）小鼠也表现出进行性视网膜变性。我们的研究结果表明，Sod 1（-/-）小鼠可能是一个很好的模型系统，在其中研究活性氧介导的视网膜变性的机制。
The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in Mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1(-/-) mice. The amplitudes of the a- and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1(-/-) mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1(-/-) mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1(-/-) and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1(-/-) mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1(-/-) mice also present progressive retinal degeneration. Our results indicate that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration.