Wip1/NF-κB负反馈环介导的星形胶质细胞炎性活化在RGCs凋亡中的作用

Astrocytes activation played an important role in the optic nerve inflammatory response. Previous studies reported that there was a potentially negative feedback loop between Wip1 and NF-κB, and we have found both Wip1 and NF-κB were in retinal astrocytes and participated in immune response. We hypothesized that the Wip1/NF-κB negative feedback loop affected the inflammatory activation in retinal astrocytes, and further regulated the inflammatory response. Our group will firstly analyze the expression, orientation and interaction of the Wip1/NF-κB negative feedback loop in retinal astrocytes in vitro and determine the existence of the negative feedback loop. Then, in the optic nerve inflammation model, we will further study the expression and interaction of Wip1/NF-κB in retinal astrocytes, and its role in the astrocytes inflammatory activation. At last, we will intervene the negative feedback loop to observe whether interrupt retinal astrocytes abnormal inflammatory response can prompt intracellular environment return to steady state equilibrium and reduce optic nerve cells apoptosis after the inflammatory response. Our study will provide the theoretical bases and molecular targets for the treatment of optic nerve diseases.

星形胶质细胞活化在视神经系统炎症反应中发挥着重要作用。文献报道Wip1和NF-κB存在相互作用，同时课题组预实验发现Wip1和NF-κB在视网膜星形胶质细胞中形成负反馈环，并参与其免疫级联反应，但其对视网膜神经节细胞（RGCs）凋亡的作用尚不清楚。为此，我们提出假说：Wip1/NF-κB负反馈环参与视网膜星形胶质细胞炎性活化，进而影响RGCs凋亡。课题组首先在体外培养的视网膜星形胶质细胞中分析Wip1和NF-κB表达、定位以及相互作用，明确Wip1/NF-κB负反馈环的存在；在此基础上,在整体和细胞水平的视神经炎症模型中，进一步研究Wip1/NF-κB负反馈环对星形胶质细胞炎性激活以及RGCs凋亡影响; 最后在整体视神经损伤模型中，干预上述调节环，观察能否通过打断星形胶质细胞异常炎症反应，减少损伤后RGCs凋亡,改善视功能。课题研究结果将为视神经系统疾病的治疗提供理论依据及分子靶点。