Retinal ganglion cell loss in superoxide dismutase 1-deficiency

超氧化物歧化酶 1 缺乏导致视网膜神经节细胞损失

• 批准号: 21791714
• 负责人: OZEKI Naoki
• 金额: $ 2.75万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791714/
• 关键词: 酸化ストレス; 緑内障; superoxide dismutase 1; 網膜神経節細胞; 網膜電図; Superoxide dismutase 1; 眼; 神経変性疾患; ノックアウトマウス

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.

目的。探讨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 (RGC) 的影响。方法。在 SOD1 完全敲除（SOD1 缺陷）小鼠中，使用二氢乙锭测量超氧阴离子水平。逆行标记后，对视网膜切片和平装视网膜中的 RGC 数量进行计数。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。进行了反映视网膜神经节细胞功能的模式视网膜电图（ERG）、暗适应ERG和锥体ERG。使用感应冲击式眼压计测量眼内压（IOP）。结果。 24周龄SOD1缺陷小鼠的RGC层超氧阴离子水平显着高于野生型小鼠。 24 周龄 SOD1 缺陷小鼠的 RGC 数量显着减少，但 8 周龄小鼠的 RGC 数量却没有显着减少。 24 周龄 SOD1 缺陷小鼠的 NFL 厚度和神经丝蛋白均减少。在 24 周龄 SOD1 缺陷小鼠中，尽管暗适应和锥体 ERG 没有表现出损害，但模式 ERG 的幅度显着降低。 SOD1 缺陷小鼠的眼压水平没有变化。

项目成果

SOD1ノックアウトマウスにおける加齢に伴う網膜神経節細胞数の変化

SOD1 敲除小鼠视网膜神经节细胞数量与年龄相关的变化

• 发表时间: 2010
• 作者: Kenya Yuki;Yoko Ozawa;Tetsu Yoshida;Toshihide Kurihara;Manabu Hirasawa;Naoki Ozeki;Daisuke Shiba;Kosuke Noda;Susumu Ishida;結城賢弥
• 通讯作者: 結城賢弥