Retinal ganglion cell loss in superoxide dismutase 1-deficiency

目的。目的：探讨视网膜神经节细胞(RGCs)中主要抗氧化酶--超氧化物歧化酶1(SOD1)缺乏对视网膜神经节细胞(RGCs)的影响。方法：研究方法。在SOD1全基因敲除(SOD1缺陷)小鼠中，用二氢乙锭测定超氧阴离子水平。逆行标记后，计数视网膜切片和平装视网膜中RGC的数量。切片测量神经纤维层厚度(NFL)，免疫印迹法检测神经丝蛋白含量。进行反映视网膜神经节细胞功能的图形视网膜电流图(ERG)、暗适应ERG和视锥ERG。用感应冲击眼压计测量眼压。结果。24周龄SOD1缺陷小鼠RGC层超氧阴离子水平显著高于野生型小鼠。24周龄SOD1缺陷小鼠的RGC数量显著减少，而8周龄小鼠的RGC数量则没有明显减少。24周龄SOD1缺陷小鼠的神经纤维层厚度和神经丝蛋白减少。在24周龄SOD1缺陷小鼠中，尽管暗适应ERG和视锥ERG没有损伤，但图形ERG的幅度显著降低。SOD1缺陷小鼠的眼压水平无明显变化。

Purpose. To investigate the influence of deficiency in superoxide dismutase 1 (SOD1), a major antioxidative enzyme, on retinal ganglion cells (RGCs). Methods. In the SOD1 total knock-out (SOD1-deficient) mice, the level of superoxide anion was measured using dihydroethidium. The number of RGCs was counted both in 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. 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.