在自发性视网膜再生中，Müller细胞去分化和增殖产生多能性祖细胞（MGPC），后者进一步增殖并分化成视网膜神经元。尽管目前对该过程中Müller细胞内在的基因表达调控已有不少研究，然而环境因素特别是炎症在视网膜再生中的作用仍不清楚。在前期研究中，我们发现抑制斑马鱼视网膜炎症可显著减少Müller细胞产生的MGPC数量，而增强炎症则出现相反效果。进一步研究发现炎症是激活Müller细胞内mTOR通路的必要和充分条件。这些结果提示炎症极可能通过激活mTOR调控视网膜再生。本课题拟利用动物模型、细胞消融、RNA测序和谱系追踪等手段，探讨炎症和mTOR在视网膜再生中的作用和关系，鉴定炎症细胞表达的关键信号分子及受体，阐明炎症激活mTOR调控视网膜再生的机制。本项目的成果有望显著加深我们对自发性视网膜再生机制的理解，并为人类的视网膜再生提供新思路和新策略。

After retina injury, teleost fish such as zebrafish are able to regenerate their damaged retina. Key to this regeneration are Müller glia that rapidly dedifferentiate and proliferate into a population of multipotent progenitor cells (MGPCs) that eventually give rise to new neurons and glia. Although the intrinsic mechanisms underlying Müller glia dedifferentiation and proliferation have been reported, little is known about the role of environmental factors, particularly inflammation, in retina regeneration. In our preliminary studies, we found acute inflammation occurred after retina injury in adult zebrafish. Suppressing retina inflammation by Dexamethasone significantly reduced the number of MGPCs, while intravitreous injection of Zymosan enhanced inflammation and resulted in more MPGCs at the injury site. Importantly, we show retina inflammation was both necessary and sufficient to activate mTOR in the Müller glia. Given the role of mTOR in the proliferation and differentiation of retina progenitor cells in other species, we hypothesize that inflammation promoted MGPC formation and retina regeneration through mTOR. In this project, we aim to utilize cell ablation, RNA sequencing and lineage tracing methods to further study the role of inflammation and downstream mTOR signaling after retina injury, identify key factors secreted by inflammatory cells and their receptors that are responsible for mTOR activation in Müller glia and MGPC formation, and eventually elucidate the molecular mechanism utilized by inflammation to enhance retina regeneration in zebrafish. Our study will not only significantly deepen our understanding of the mechanisms underlying a successful retina regeneration, but also provide new insights and strategies to the future regeneration of a human retina.