The Role Of Inflammation And Downstream MTOR Signaling In Zebrafish Retina Regeneration

Inflammation and tissue regeneration have close and complicate relations.However,the role of inflammation in retina regeneration remains unclear.In this study,we investigated the role of inflammation and m TOR signaling in zebrafish retina regeneration.We found that in three different models of retina regeneration in adult zebrafish,various degrees of inflammation mediated by IB4+ microglia occurred in the retina.Importantly,suppressing retina inflammation with Dexamethasone significantly reduced the number of Müller glia-derived progenitor cells(MGPCs)and new born retinal neurons.In contrast,enhancing retina inflammation by intravitreous injection of Zymosan A significantly promoted MGPC formation and their differentiation.We further show inflammation was necessary and sufficient to activate m TOR in the Müller glia and it promoted retina regeneration through m TOR.Finally we performed a preliminary screening of microglia-secreted cytokines and growth factors that may be involved in m TOR activation in Müller glia.Together,our study revealed a critical role of inflammation and downstream m TOR signaling in zebrafish retina regeneration.Findings from this study not only significantly deepen our understanding of retina regeneration in fish,but also suggest novel strategies in the future repair of a mammalian retina.