P2X7受体在慢性高眼压视网膜Müller细胞介导的神经炎症反应中的作用及机制研究

项目名称： P2X7受体在慢性高眼压视网膜Müller细胞介导的神经炎症反应中的作用及机制研究

项目编号： No.81670852

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 季敏

作者单位： 南通大学

项目金额： 25万元

中文摘要： 青光眼是重要的致盲性神经退行性眼病，Müller细胞是视网膜最主要的胶质细胞。我们前期研究发现Müller细胞在青光眼条件下被激活，并且可导致神经节细胞死亡，但具体机制未完全阐明。近期研究发现，胶质细胞参与的神经炎症与神经变性疾病发生发展密切相关。P2X7受体是调控神经系统与免疫系统的桥梁，与炎症小体激活、自噬等炎症相关反应密切相关。我们前期研究证实Müller细胞表达该受体，高眼压时表达增加，并且该受体激活可导致IL-1β表达增加。因此，我们提出的假设是，慢性眼压增高，P2X7受体被激活，进而影响NLRP3炎症小体、细胞自噬、焦亡，介导神经炎症，最终导致神经节细胞死亡。为此，本课题拟采用体内及体外实验，利用电镜、膜片钳、免疫组织化学、免疫共沉淀、流式细胞技术、Western blot、ELISA等多种技术，探讨P2X7受体在高眼压视网膜Müller细胞神经炎症反应中的作用及机制。

中文关键词： 神经炎症；P2X7受体；Müller细胞；视网膜神经节细胞损伤；青光眼

英文摘要： Glaucoma is an important neurodegenerative disease, and Müller cells are the main glial cells of retina. Our preliminary data showed that Müller cells were activated in glaucoma, and finally cause RGC death with an unclarified mechanism. Up to date, glial cell neuroinflammation was notably involved in neurodegenerative disease. P2X7 receptors was thought to be the key role in regulating interaction of the immune system and nervous system. Our previous data also showed that P2X7 receptors expressed in retinal Müller cells and increased with the progression of high introcular pressure. BzATP, the antagonist of P2X7 receptors, increased the expression of IL-1β in Müller cells. Therefore, we hypothesized that over-activation of P2X7 receptors by high introcular pressure in the rat chronic intraocular hypertension (COH) triggers Müller cell neuroinflammation, including activation of NLRP3 inflammasome, disorder of autophage and downregulation the function of lysosome, and finally cause RGC death. Our proposal aims to study the involvement of P2X7 receptors in Müller cell neuroinflammation in the COH, and to explore the underlying mechanisms by using electron microscope, whole-cell patch-clamp, immunohistochemistry, Western blot, co-immunoprecipitation, ELISA and flow cytometry.

英文关键词： neuroinflammation;P2X7 receptor;Müller cell;RGC injury;glaucoma