Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2019 Sep 3;60(12):3696-3707. doi: 10.1167/iovs.19-27145.
We assess if α retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma.
Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma.
NMDA-induced loss of RBPMS-positive total RGCs was 58.4% ± 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive αRGCs was 5.0% ± 0.6% and that of melanopsin-positive ipRGCs was 7.6% ± 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% ± 0.9% compared to wild-type mice, whereas the loss of αRGCs and ipRGCs was 3.9% ± 0.4% and 9.3% ± 0.5%, respectively. The distribution of survived total RGCs, αRGCs, and ipRGCs was similar regardless of the location of the retina.
These results suggest that αRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.
我们评估在青光眼的小鼠模型中，α 视网膜神经节细胞（αRGCs）和内在光敏视网膜神经节细胞（ipRGCs）是否存活。
在处死前 7 天，通过眼内注射 2μl N-甲基-D-天冬氨酸（NMDA；1mM）或 PBS。使用针对 RNA 结合蛋白多剪接（RBPMS）、骨桥蛋白和黑视素的抗体对视网膜进行免疫组织化学分析。还对谷氨酸/天冬氨酸转运体（GLAST）缺失（GLAST 敲除 [KO] 小鼠）的成年小鼠，即正常眼压型青光眼的小鼠模型，进行了免疫组织化学分析。
与 PBS 处理的对照组相比，NMDA 诱导的 RBPMS 阳性总 RGC 丧失率为 58.4%±0.4%，而骨桥蛋白阳性 αRGC 丧失率为 5.0%±0.6%，黑视素阳性 ipRGC 丧失率为 7.6%±1.6%。在 GLAST KO 小鼠中，与野生型小鼠相比，总 RGC 的丧失率为 48.4%±0.9%，而 αRGC 和 ipRGC 的丧失率分别为 3.9%±0.4%和 9.3%±0.5%。存活的总 RGC、αRGC 和 ipRGC 的分布无论在视网膜的哪个位置都相似。
这些结果表明，αRGC 和 ipRGC 对 NMDA 诱导的神经毒性和 GLAST KO 小鼠的 NTG 样神经退行性变具有高度耐受性。
