视网膜缺血再灌注（I/R）损伤是许多重要致盲眼病的关键致病机制，目前缺乏有效治疗手段。小胶质细胞极化介导的炎症反应是I/R继发神经细胞死亡的重要环节。我们前期研究发现，I/R模型中，骨髓间充质干细胞（BMMSCs）外泌体miR-21含量增多，并能在体内抑制小胶质细胞活化，保护视网膜损伤。抑制miR-21后BMMSCs外泌体的视网膜保护作用明显减弱。因此我们提出设想：BMMSCs外泌体中的miR-21是关键因子，可能经由其靶蛋白PDCD4，调控小胶质细胞极化信号，减轻炎症毒性，保护视网膜神经细胞损伤。为了验证这一设想，我们将通过建立小鼠视网膜I/R模型及体外小胶质细胞氧糖剥夺再灌注（OGDR）模型，从基因、分子和细胞水平，探讨BMMSCs通过外泌体传递miR-21，实现免疫调节介导的神经保护作用机制。希望通过此课题研究找到视网膜I/R损伤保护的新靶点，为重要致盲眼病的治疗找到新方向。

The retina ischemia-reperfusion (I/R) injury is the critical pathogenic mechanism of many important blinding eye diseases, which are the lack of effective treatment at present. Microglia polarization mediated inflammatory reaction plays an important role in the I/R secondary neuronal cell death. In our previous research, in the I/R model, increased miR – 21 in bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes was found, and BMMSCs-derived exosomes can restrain the microglia activation and protect retinal damage. Inhibition of miR-21, BMMSCs exosomes showed less protective effect for retina I/R injury. So we put forward the hypothesis: BMMSCs-derived exosomes can deliver miR - 21 as the key factor to target protein PDCD4, as to regulate microglia polarization signal, reduce inflammation toxicity and protect the retina neural cell damage. To verify this hypothesis, we will establish the mouse retina I/R model in vivo and microglia oxygen deprived of reperfusion (OGDR) model in vitro, based on genetic, molecular and cellular level, discover how BMMSCs-derived exosomes deliver miR-21 to achieve immunomodulation mediated neuroprotection. Hope that through this project, we will find a new target for retinal I/R injury protection and a new direction for developing important blinding eye disease treatment.