TXNIP介导早期糖尿病视网膜病变RGC细胞自噬和凋亡的调控机制

细胞自噬和凋亡之间的平衡状态是机体自我保护的重要机制，硫氧还蛋白内源性抑制蛋白（TXNIP）可通过多种途径调控细胞自噬和凋亡。文献报道和我们的前期研究证实：TXNIP在RGC受到高糖应激损伤的早期即迅速升高并在糖尿病视网膜病变（DR）过程中持续高表达，且伴随神经节细胞（RGC）凋亡和自噬，但是TXNIP在早期DR中的具体调控机制尚未明确。本项目拟首先在糖尿病大鼠模型和体外高糖/低氧损伤的RGC中分别检测TXNIP、自噬和凋亡信号分子的时空表达，并与相应的视网膜应激水平相对应；然后在早期DR不同病理损伤阶段，通过阻断性抗体、RNA干扰或TXNIP抑制剂TGS等多种手段下调TXNIP，观察其对于RGC自噬和凋亡的调控机制，最终筛选出适合早期糖尿病应激损伤的RGC保护性调控策略。通过本研究，有望为DR的早期视神经保护提供实验依据和理论基础。

The balance between cellular autophagy and apoptosis is an important mechanism to maintain homeostasis. Recently, thioredoxininteracting protein (TXNIP) has been shown to be an upstream checkpoint to modulate the balance between cellular autophagy and apoptosis through a series of signal pathways. Literatures and our previous work showed that TXNIP is significantly upregulated upon high glucose induced stresses, and maintained over the whole process of diabetic retinopathy (DR). But the detailed mechanism remains unknown. In this project, we plans to use high glucose challenged rat retina and primarily cultured retinal ganglion cells (RGCs) to evaluate the expression of TXNIP, and autophagy- and apoptosis-related markers in different stages of applied stress. At the mean while, we will use blocking antibody, RNA interference, or inhibitor TGS to down regulate TXNIP, in order to select the optimal protective effects on RGC. This study might provide new strategy for neural protection in early DR.