TRF2是端粒保护蛋白，可通过端粒外效应调控基因表达。申请人首次发现TRF2+/-斑马鱼感光细胞退行性改变且视网膜再生能力下降，机制不清。二代测序发现，TRF2+/-斑马鱼Müller细胞重编程相关基因表达改变。Müller细胞是视网膜再生的主力军，可抑制感光细胞退行性改变，故此我们推测TRF2可通过端粒外效应调控Müller细胞功能，抑制感光细胞退行性改变。课题通过多种手段观察TRF2+/-斑马鱼Müller细胞重编程的改变；通过RNA Seq、ChIP Seq及单细胞测序探讨TRF2对Müller细胞功能的调控机制及具体靶点，明确Müller细胞抑制感光细胞退行性改变的重要机理，阐明TRF2调控Müller细胞重编程的具体机制。课题的完成将加深对Müller细胞调控网络的理解，有助于发现干预感光细胞退行性改变的新靶点，也将丰富对TRF2端粒外效应的认识，对理解全身衰老机制有着深远意义。

TRF2 is an essential protein required for telomeres protection, which plays a vital role in regulating gene expression through extratelomeric effect. In the present study, we found that TRF2 deficiency induce photoreceptor degeneration and decreased regeneration in TRF2+/- zebrafish. However, the underlying mechanisms remain elusive. Next generation sequencing (NGS) revealed that the expression of genes associated with cell reprogramming are significantly changed in the Müller glia cells of TRF2+/- zebrafish retina. Müller glia cells possess potential neurogenic properties, It is well known that Müller cells is an important participant in retinal repair photoreceptor cells (RRPCs), we speculate that the injured photoreceptor cells can be repaired via Müller cells reprogramming and this reprogramming is regulated by TRF2 controlled extra-telomeric roles. The study proposed above may illuminate the impact of dysfunction of Müller glia cells on photoreceptor degeneration and clarify how TRF2 modulates Müller glia function, which could expose new insights into the mechanism underlying Müller glia reprogramming and identify novel targets and pathways to prevention and treatment of photoreceptor degeneration.