Kobayashi Mamoru, Hirooka Kazuyuki, Ono Aoi, Nakano Yuki, Nishiyama Akira, Tsujikawa Akitaka
Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
Department of Pharmacology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1397-1403. doi: 10.1167/iovs.16-21001.
Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death.
N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits.
A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection.
Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.
兴奋性毒性是视网膜神经节细胞（RGC）丧失的几种机制之一，其由谷氨酸对RGC的毒性作用引起。肾素-血管紧张素-醛固酮系统（RAAS）也与RGC死亡有关。因此，确定RAAS与N-甲基-D-天冬氨酸（NMDA）受体介导的信号之间的确切关系对于预防RGC死亡很重要。
将N-甲基-D-天冬氨酸或醛固酮注入玻璃体。在玻璃体内注射NMDA或醛固酮后，用螺内酯或美金刚治疗动物。通过在局部给予醛固酮4周后或局部给予NMDA 2周后测量RGC的数量来评估视网膜损伤。使用酶免疫分析试剂盒测量玻璃体液中醛固酮的水平。
玻璃体内注射NMDA后观察到RGC数量显著减少。虽然螺内酯未显示出任何神经保护作用，但美金刚显著减少了NMDA诱导的视网膜变性。此外，玻璃体内注射醛固酮后观察到RGC数量显著减少。虽然美金刚未表现出任何神经保护作用，但螺内酯显著减少了醛固酮诱导的视网膜变性。NMDA注射后玻璃体液中醛固酮浓度没有变化。
我们的研究结果间接表明，在RGC死亡方面，RAAS与NMDA受体介导的信号之间没有关系。
