抗视网膜神经节细胞(RGCs)凋亡是防治糖尿病视网膜病变(DR)的关键。MBD2是调控DNA甲基化的重要基因，其参与凋亡调控，但对RGCs凋亡的作用及机制不清。本项目拟采用高糖诱导的RGCs凋亡和链脲菌素(STZ)诱导的糖尿病(DM)小鼠模型，探讨MBD2调控RGCs凋亡的作用及机制。预实验结果发现：MBD2 siRNA干预后，高糖诱导的RGCs凋亡减少、Bax及caspase活性显著下降, 进一步通过miRs芯片表达谱、实时PCR和Northern blot等手段揭示其显著下调了miR-708-5p和-345-5p表达。因此，本项目拟深入探讨抑制MBD2下调高糖诱导上述miRs的分子机制，揭示上述miRs分别通过调控直接靶基因NNAT和MDM4促RGCs凋亡的信号机制，并使用MBD2敲除小鼠构建DM模型揭示其抗RGCs凋亡的机理，为抑制MBD2抗DR提供科学的理论依据和防治新靶点。

Apoptosis of retinal ganglion cells (RGCs) is an early event in the pathogenesis of diabetic retinopathy. MBD2 plays an important role in the regulation of DNA methylation. Recent studies demonstrate that MBD2 is involved in apoptosis regulation, however，its exact role in RGCs remains unclear. To explore the underlying mechanisms of MBD2 in the regulation of apoptosis in RGCs, both high glucose-induced apoptosis of RGCs and streptozotocin-induced diabetic mice were used in the project. In our previous studies, we observed the Bax and caspase activation in RGCs undergoing high glucose-induced apoptosisis significantly decreased after the MBD2 siRNA intervention as well as the decreasing number of apoptotic RGCs. Furthermore, the level of miR-708-5p and -345-5p was found significantly down-regulated after MBD2 siRNA transfection, which was confirmed by Real-Time PCR and Northern blot analysis. Therefore, the purpose of our project is to clarify the molecular mechanism underlying the above miRs in promoting RGCs apoptosis via regulating the target genes NNAT and MDM4 respectively. And we would make use of the MBD2-knockout mouse to clarify its function of anti-apoptosis in RGCs, thus providing a novel therapeutic strategy for DR.