Retinal ganglion cell loss in superoxide dismutase 1 deficiency.
Retinal ganglion cell loss in superoxide dismutase 1 deficiency.
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DOI：
10.1167/iovs.10-6294
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发表时间：
2011-06
影响因子：
4.4
通讯作者：
K. Yuki;Y. Ozawa;Tetsu Yoshida;T. Kurihara;Manabu Hirasawa;Naoki Ozeki;D. Shiba;K. Noda;S. Ishida;K. Tsubota
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文献类型：
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作者：
K. Yuki;Y. Ozawa;Tetsu Yoshida;T. Kurihara;Manabu Hirasawa;Naoki Ozeki;D. Shiba;K. Noda;S. Ishida;K. Tsubota
目的探讨主要抗氧化酶超氧化物歧化酶（SOD）1缺乏对视网膜神经节细胞（RGCs）的影响。方法用二氢乙锭法测定SOD 1基因敲除小鼠体内超氧阴离子水平。逆行标记后，在视网膜切片和平片视网膜中计数RGC的数量。在切片中测量神经纤维层（NFL）的厚度，并通过免疫印迹分析测量神经丝蛋白的量。进行反映视网膜神经节细胞功能的图形视网膜电图（ERG）、暗适应ERG和视锥ERG检查。用感应冲击式眼压计测量眼压。采用酶联免疫吸附法（ELISA）检测47例正常眼压性青光眼（NTG）患者和44例正常对照者血清中SOD-1和SOD-2的含量。结果24周龄SOD 1缺陷小鼠视网膜神经节细胞层超氧阴离子水平显著高于野生型小鼠。24周龄SOD 1缺陷小鼠的RGC数量显著减少，但8周龄小鼠的RGC数量没有减少。NFL厚度和神经丝蛋白在24周龄SOD 1缺陷小鼠中减少。在24周龄SOD 1缺陷小鼠中，模式ERG的幅度显著降低，尽管暗适应和视锥ERG没有显示出损害。SOD 1缺陷小鼠的IOP水平没有变化。NTG患者血清SOD 1水平显著低于健康对照组，而SOD 2水平无显著差异。结论SOD 1缺陷导致RGC的易损性，可能参与NTG的基础疾病。
PURPOSE To investigate the influence of deficiency in superoxide dismutase (SOD) 1, a major antioxidative enzyme, on retinal ganglion cells (RGCs). METHODS In the SOD1 total knockout (SOD1-deficient) mice, the level of superoxide anion was measured using dihydroethidium. The number of RGCs was counted in both the retinal sections and the flat-mount retinas after retrograde labeling. Thickness of nerve fiber layer (NFL) was measured in the sections, and the amount of neurofilament protein was measured by immunoblot analysis. Pattern electroretinogram (ERG), which reflects the function of retinal ganglion cells, dark-adapted ERG, and cone ERG were performed. The intraocular pressure (IOP) was measured with an induction-impact tonometer. The levels of SOD-1 and -2 were measured by ELISA, in the serum of 47 newly diagnosed consecutive normal tension glaucoma (NTG) patients and 44 consecutive control subjects. RESULTS The level of superoxide anion in the RGC layer was significantly higher in 24-week-old SOD1-deficient mice than in wild-type mice. The RGC number was significantly reduced in 24-week-old SOD1-deficient mice, although they were not in 8-week-old mice. The NFL thickness and neurofilament protein were reduced in 24-week-old SOD1-deficient mice. The amplitude of pattern ERG was significantly reduced, although dark-adapted and cone ERGs showed no impairment, in 24-week-old SOD1-deficient mice. The IOP level was not changed in the SOD1-deficient mice. The serum level of SOD1, but not SOD2, was significantly lower in the NTG patients than in the healthy controls. CONCLUSIONS SOD1 deficiency causes RGC vulnerability, which may be involved in the underlying condition of NTG.