视网膜脱离后TNF-α对光感受器细胞自噬的调控作用研究

光感受器细胞死亡是视网膜脱离、年龄相关性黄斑变性、视网膜色素变性等很多致盲性眼病的共同病理改变，是导致视力丧失的关键因素，这些疾病光感受器细胞死亡的机制不清。视网膜脱离是研究光感受器细胞死亡的理想模型，以往的研究多集中在凋亡方面，但是即便阻止凋亡的发生也不能完全保护光感受器细胞的丢失。近年研究发现自噬在光感受器细胞的生存和死亡中发挥着重要的作用，自噬可以保护细胞，但是过多的自噬又可以导致细胞死亡。而且TNF-α、IL-2、IL-6等炎性因子在视网膜脱离后光感受器细胞的自噬中具有一定的调节作用。本研究拟利用视网膜脱离的动物模型和培养的光感受器细胞损伤模型，研究光感受器细胞自噬的发生，以及与细胞存活和死亡方式的关系，并试图通过调控视网膜脱离后TNF-α的表达，改变自噬的进程，探讨视网膜脱离后光感受器细胞的自噬从细胞保护转化成细胞死亡的机制，进一步探讨视网膜脱离后光感受器细胞保护策略。

Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD), age-related macular degeneration, retinitis pigmentosa. The photoreceptor death plays critical role in the blindness causation but the mechanism is still unclear. Retinal detachment is the ideal model to investigate the photoreceptor death.Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. But anti-apoptosis could not prevent the photoreceptor death thoroughly. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy, also regulates the photoreceptor death. Autophagy can protect photoreceptors from death, but over activated autophagy will cause cell death. The inflammation factors, such as, TNF-alpha, IL-2, IL-6, were involved in the photoreceptor autophagy after retinal detachment.In this study, we will use retinal detachment animal model and cultured photoreceptor cells, to study the autophagy both in vivo and in vitro, and to investigate its effect in photoreceptor death.We will clarify the pathology of photoreceptor death after retinal detachment through intervention of autophagy and TNF-αexpression by Atg5 knockout mice and medications. And further，look for efficient way to improve the strategy for photoreceptor protection after retinal detachment.