Cav-1调控小胶质细胞极化在青光眼中的神经保护作用及分子机制

青光眼是以视网膜神经节细胞(RGCs)凋亡为病理基础的疾病，有效保护RGCs是青光眼的防治核心。然而，目前尚无针对青光眼RGCs损伤的有效治疗手段。我们既往研究及前期结果发现，Cav-1在小鼠急性高眼压模型中减缓RGCs凋亡；促进视网膜小胶质细胞（MG）由M1（炎症）向M2（修复）极化表型的转化；Cav-1在极化的MG中会激活Akt/PTEN通路。本课题拟建立体内体外青光眼模型，结合细胞、分子生物学及免疫荧光等方法，从形态及功能明确Cav-1对视神经的保护作用；探索Cav-1是否通过对MG极化调控而保护RGCs；利用中和抗体、shRNA和抑制剂验证Akt/PTEN是否为Cav-1调控MG极化的机制；利用芯片技术挖掘Cav-1潜在下游靶点；最后利用临床标本验证Cav-1及筛选靶点的表达及与青光眼病程的相关性。本研究将阐明Cav-1在青光眼神经保护中的作用及机制，为青光眼防治提供新思路。

The pathological basis of glaucoma is retinal ganglion cells (RGCs) apoptosis, the core of prevention and treatment of glaucoma are effective protection of RGCs. However, there is no effective treatment for RGCs damage in glaucoma. In previous studies, we found that Cav-1 has neuroprotective effects in an acute ocular hypertension model, and promotes the transformation of retinal microglia from M1（inflammation） to M2（protection） polarized phenotypes. Cav-1 activated Akt / PTEN signaling pathway in polarized microglia cell lineage. This project aims to establish an in vitro and in vivo glaucoma model, combining cell, molecular biology and immunofluorescence, to clarify the protective effect of Cav-1 on optic nerve from morphology and function；To explore whether Cav-1 protects RGCs by regulating MG Polarization; Using neutralized antibodies, RNAi and inhibitors to verify whether Akt/PTEN is the mechanism of Cav-1 regulates MG polarization; Exploiting potential downstream targets of Cav-1 using chip technology; Finally, use of clinical specimens to verify the expression of Cav-1 and screening targets and its correlation with the course of glaucoma. This study will clarify the role and mechanism of Cav-1 in the neuroprotection of glaucoma and provide new ideas for the prevention and treatment of glaucoma.