环状RNA RRCR靶向吸附miR-26a经CD200信号轴调控神经炎症和RGCs凋亡的分子机制

小胶质细胞介导的神经炎症可导致视网膜神经节细胞（RGCs）凋亡。课题组前期研究证实CD200信号轴通过调控小胶质细胞和RGCs间“接触抑制”效应参与上述过程，但内源性调控机制尚不清楚。国内外研究提示，miRNA能在转录和翻译水平调控基因表达，且环状RNA可靶向吸附miRNA。我们预实验得到可调控CD200信号轴的候选环状RNA RRCR和miRNA miR-26a。基于此提出假说：RRCR靶向吸附miR-26a可经CD200信号轴调控视网膜神经炎症和RGCs凋亡。课题组拟首先明确CD200通路参与神经炎症和RGCs凋亡；在此基础上，分析miR-26a与CD200结合的分子位点和调控方式；同时检验RRCR的环状结构及其对miR-26a靶向吸附效应；最终通过靶向干预RRCR，观察其对miR-26a及其下游CD200信号轴的影响。研究成果将为视网膜退行性疾病提供新的治疗靶点和理论基础。

Microglia-mediated neuroinflammation leads to retinal ganglion cells (RGCs) apoptosis. Our prior researches confirmed that CD200 and its receptor CD200R1 participated in the above process via regulating the “contact inhibition” between microglia and RGCs, but the molecular mechanism is still unclear. Previous researches suggest that circular RNA acts as miRNA sponge regulate gene expression at the transcription and translation levels. We found that circular RNA RRCR and miRNA miR-26a were the candidate gene of targeting CD200 signal axis. We hypothesized that RRCR acts as miR-26a sponge to regulate retinal neuroinflammation and RGCs apoptosis via modulating the CD200 signal axis. Our previous researches confirmed that CD200 signal axis participated in neuroinflammation and RGCs apoptosis. Based on this, we analyzed the binding sites and regulation method between miR-26a and CD200 and the RRCR ring structure sponged miR-26a. Finally, to observe the effect on miR-26a and its downstream CD200 signaling pathway via targeting intervention in RRCR, our study will provide the theoretical bases and molecular targets for the treatment of retinal degenerative diseases.