The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.
The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.
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DOI：
10.1167/iovs.16-21001
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发表时间：
2017-03
影响因子：
4.4
通讯作者：
Mamoru Kobayashi;K. Hirooka;Aoi Ono;Yuki Nakano;A. Nishiyama;A. Tsujikawa
中科院分区：
文献类型：
--
作者：
Mamoru Kobayashi;K. Hirooka;Aoi Ono;Yuki Nakano;A. Nishiyama;A. Tsujikawa
目的
兴奋性毒性是视网膜神经节细胞（RGC）丢失的几种机制之一，它是由谷氨酸对RGC产生的毒性作用导致的。肾素 - 血管紧张素 - 醛固酮系统（RAAS）也与RGC死亡有关。因此，为了预防RGC死亡，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非常重要。
方法
将N - 甲基 - D - 天冬氨酸或醛固酮注射到玻璃体中。在玻璃体内注射NMDA或醛固酮后，用螺内酯或美金刚对动物进行治疗。通过测量局部给予醛固酮4周后或局部给予NMDA 2周后的RGC数量来评估视网膜损伤。使用酶免疫测定试剂盒测量玻璃体液中醛固酮的水平。
结果
玻璃体内注射NMDA后，观察到RGC数量显著减少。尽管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，但螺内酯使醛固酮诱导的视网膜变性显著减少。注射NMDA后，玻璃体液中的醛固酮浓度没有变化。
结论
我们的研究结果间接表明，就RGC死亡而言，RAAS与NMDA受体介导的信号之间没有关系。
Purpose 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. Methods 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. Results 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. Conclusion Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.