Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration.
Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration.
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DOI：
10.3390/life12050638
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发表时间：
2022-04-25
期刊：
影响因子：
3.2
通讯作者：
Fairless, Richard
中科院分区：
文献类型：
--
作者：
Boccuni, Isabella;Fairless, Richard
谷氨酸神经传递和代谢由视网膜网络精细调节，其中视觉信息的有效处理由谷氨酸受体和转运蛋白的差异分布和组成形成。然而，谷氨酸稳态的紊乱可导致谷氨酸兴奋性毒性，这是常见神经退行性疾病的主要起始因素。在视网膜内，谷氨酸兴奋性毒性可通过引发神经元群体（包括视网膜神经节细胞（RGC））的变性而损害视觉传递。观察到RGCs的脆弱性不仅是视网膜疾病的结果，而且还归因于其他常见的神经退行性疾病和外周疾病。在这篇综述中，我们描述了RGCs对谷氨酸兴奋性毒性的脆弱性以及不同谷氨酸受体和转运蛋白对此的贡献。特别是，我们专注于N-甲基-D-天冬氨酸（NMDA）受体作为谷氨酸诱导的神经退行性变机制的主要效应子，包括钙稳态受损，基因表达和信号转导的变化，线粒体功能障碍，以及内质网应激的作用。由于最近的发展，在寻找NMDA受体信号转导的调制器，新的神经保护策略可能是在地平线上。
Glutamate neurotransmission and metabolism are finely modulated by the retinal network, where the efficient processing of visual information is shaped by the differential distribution and composition of glutamate receptors and transporters. However, disturbances in glutamate homeostasis can result in glutamate excitotoxicity, a major initiating factor of common neurodegenerative diseases. Within the retina, glutamate excitotoxicity can impair visual transmission by initiating degeneration of neuronal populations, including retinal ganglion cells (RGCs). The vulnerability of RGCs is observed not just as a result of retinal diseases but has also been ascribed to other common neurodegenerative and peripheral diseases. In this review, we describe the vulnerability of RGCs to glutamate excitotoxicity and the contribution of different glutamate receptors and transporters to this. In particular, we focus on the N-methyl-d-aspartate (NMDA) receptor as the major effector of glutamate-induced mechanisms of neurodegeneration, including impairment of calcium homeostasis, changes in gene expression and signalling, and mitochondrial dysfunction, as well as the role of endoplasmic reticular stress. Due to recent developments in the search for modulators of NMDA receptor signalling, novel neuroprotective strategies may be on the horizon.
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DOI：
10.4172/2155-9899
发表时间：
2013
期刊：
Journal of clinical & cellular immunology
影响因子：
--
作者：
Abcouwer SF
通讯作者：
Abcouwer SF
影响因子：
4.6
作者：
Asanad S;Felix CM;Fantini M;Harrington MG;Sadun AA;Karanjia R
通讯作者：
Karanjia R
影响因子：
2.5
作者：
Brandstätter, JH;Dick, O;Boeckers, TM
通讯作者：
Boeckers, TM
DOI：
10.1084/jem.20161673
发表时间：
2017-03-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bading H
通讯作者：
Bading H
影响因子：
4.1
作者：
Andrews, RM;Griffiths, PG;Turnbull, DM
通讯作者：
Turnbull, DM