基于酸敏感离子通道调控视网膜神经节细胞损伤过程的青光眼发病机制及治疗研究

项目名称： 基于酸敏感离子通道调控视网膜神经节细胞损伤过程的青光眼发病机制及治疗研究

项目编号： No.81200681

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 谭健

作者单位： 同济大学

项目金额： 23万元

中文摘要： 青光眼导致的视网膜神经节细胞（RGCs）损伤过程中伴有组织酸化，其可通过酸敏感离子通道（ASICs）对RGCs等神经元细胞进行直接损伤。研究表明ASICs参与中枢神经系统缺血等由谷氨酸释放和酸中毒所导致的神经元死亡。同时，本课题组在前期研究中已证明：ASICs在RGCs中表达，且以异聚体（ASIC1a、ASIC3）的形式存在；酸化引起的由ASICs介导的酸电流，可导致RGCs细胞内Ca2+浓度升高，其酸电流在氰化钠处理后增加明显。因此，ASICs在RGCs病理改变中发挥重要的作用。本课题设计采用ASIC1a基因敲除小鼠建立慢性高眼压性青光眼模型、自发性青光眼模型DBA/2J小鼠以及体外培养的RGCs细胞等，研究ASICs在青光眼RGCs损伤过程中的作用及机制，从离子通道的角度丰富青光眼视功能损伤的理论，并为针对青光眼RGCs损伤的保护及药物开发提供新的靶点。

中文关键词： 酸敏感离子通道；视网膜神经节细胞；青光眼；依达拉奉；视网膜色素上皮细胞

英文摘要： Glaucoma is a group of diseases characterized by progressive optic nerve degeneration that results in visual field loss and irreversible blindness. A crucial element in the pathophysiology of all forms of glaucoma is the death of retinal ganglion cells (RGCs), a population of CNS neurons with their soma in the inner retina and axons in the optic nerve. The conduction of acid-evoked currents in central and sensory neurons is now primarily attributed to a family of proteins called acid-sensing ion channels (ASICs). ASICs are mainly expressed in the central and peripheral nervous systems, where they form homomultimeric and heteromultimeric cation channels. Moreover, the homomeric channel composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. In the retina, recent data have suggested that pH fluctuations play an important role in pathological conditions such as ischemia. There has been speculation about the physiologic and pathophysiological function of acid-gated currents in central neurons. So we hypothesize that interstitial acidosis associated with seizures and ischemia in glaucoma could trigger their activity, thereby exacerbating the pathological consequences of these conditions. Our previous studies have demonstrated that, first

英文关键词： acid-sensing ion channels；retinal ganglion cells；glaucoma；edaravone；retinal pigment epithelial cells