间充质干细胞来源的lncRNATGFβR1和miRNA-27a-3p靶向作用于TGFβR1改善抑制性微环境促进视神经再生的机制

因内源性再生能力不足和外源抑制性微环境存在，成体RGCs受损后逐渐死亡且不能自发性再生是青光眼的病理改变。干细胞对RGCs外源抑制性微环境的作用不明；TGFβ信号通路过度活化在构造外源抑制性微环境过程中起关键作用；lncRNATGFβR1与青光眼患者的病程密切相关。预实验显示，MSCs上清液可有效减低受损细胞对TGFβ信号通路的敏感度，持续性分泌lncRNATGFβR1和miRNA-27a-3p。故假设：MSC中的lncRNATGFβR1可通过“捕获”及“释放”miRNA-27a-3p，调控TGFβR1表达水平，改善抑制性微环境而促进视神经再生。我们将从TGFβ信号通路下游的经典及非经典Smad通路入手，通过体外及体内实验，全面探讨MSCs来源lncRNATGFβR1和miRNA-27a-3p靶向作用TGFβR1解除抑制性微环境对RGCs影响的相关机制，为视神经再生治疗提供强有力的依据。

The pathological characteristics of glaucoma are the death of adult retinal ganglion cells (RGCs) and failure of axon regeneration, which are attributed to inhibitory microenvironment and an insufficient intrinsic ability to regrow axons after injury. It remains elucidated how mesenchymal stem cells (MSCs) activities affect the inhibitory microenvironment. The over-activity of TGFβ signal pathway plays the key role in establishing inhibitory microenvironment. Moreover, lncRNA TGFβR1 is shown to be strongly correlated with the clinical course of glaucoma patients. Our experiment results demonstrate that MSCs are able to persistently secret lncRNA TGFβR1 and miRNA-27a-3p into the supernatant which could desensitize damaged cells to TGFβ signal pathway. Therefore, our hypothesis is MSCs derived lncRNA TGFβR1 could improve inhibitory microenvironment and induce optic nerve regeneration through targeting TGFβR1 via sponging and releasing miRNA-27a-3p. To elucidate the mechanism of how MSCs derived lncRNA TGFβR1 and miRNA-27a-3p induce optic nerve regeneration, we will focus on TGFβ signal pathway related canonical Smad pathway and noncanonical Smad pathway in vitro and in vivo. Hopefully, we will provide a strong basis for the treatment of optic nerve regeneration.