谷氨酸受体在试验性青光眼视网膜细胞损伤中的作用-生理学报.PDF

生理学报Acta Physiologica Sinica , August 25, 2016, 68(4): 483–491 483 DOI: 10.13294/j.aps.2016.0030 综　述 谷氨酸受体在实验性青光眼视网膜细胞损伤中的作用 * 王中峰 ，杨雄里 复旦大学脑科学研究院，神经生物学研究所，上海市视觉损害与重建重点实验室，医学神经生物学国家重点实验室，脑科 学协同创新中心，上海 200032 摘 要：青光眼是第二大致盲性眼病，为不可逆致盲的最主要原因。视网膜神经节细胞损伤和死亡是青光眼所致视功能损害 的根本原因。在青光眼视神经损伤的众多病理过程中，谷氨酸受体功能的改变是导致神经节细胞凋亡的重要因素。本研究 组在大鼠慢性高眼压实验性青光眼模型上，围绕这一主题开展了一系列研究。研究结果表明，一方面，高眼压导致的众多 信号变化通过直接调控谷氨酸的NMDA和AMPA受体功能参与神经节细胞的凋亡过程；另一方面，高眼压导致的细胞外谷氨 Müller I (group I metabotropic glutamate receptors, mGluR I) Kir4.1 酸集聚激活 细胞上的 型代谢型谷氨酸受体 ，经下调细胞膜的 钾 通道引发Müller细胞的胶质化激活，进而导致神经节细胞的凋亡。结合这些结果，本文综述了有关谷氨酸受体在实验性青光 眼视网膜细胞损伤中的作用及机制的若干研究进展。 关键词：青光眼；视网膜；Müller 细胞；胶质化激活；神经节细胞凋亡 中图分类号：R339.14+6 ；R775.9 Glutamate receptor-mediated retinal neuronal injury in experimental glaucoma * WANG Zhong-Feng , YANG Xiong-Li Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Key Laboratory of Visual Impairment and Restoration, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China Abstract: Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, func- tional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model. We demonstrated that elevated intraocular pressure in COH rats may induce changes of various signaling pathways, which are involved in RGC apoptosis by modulating glutamate NMDA and AMPA receptor