mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish

Zebrafish is capable of endogenously regenerating functional retina pigment epithelium (RPE) after widespread genetic ablation which involves a series of cellular and molecular events that remain to be defined. Here, using the RPE genetic ablation model in zebrafish, we observed that mTOR signaling was activated in the RPE cells post-ablation. Pharmacological and genetic inhibition of mTOR signaling impaired RPE regeneration, while activation of mTOR signaling benefited RPE recovery, suggesting mTOR signaling was required and sufficient for RPE regeneration post-ablation in zebrafish. We further identified an interesting crosstalk between mTOR signaling and microglia/macrophages during RPE regeneration that mTOR acts as an upstream regulator of microglia/macrophage infiltration to the injury site while microglia/macrophage, in turn, rainenforce mTOR activity. Overall design: RNA-seq of FACS-purified retinal pigment epithelium from ablated and unbalted rapamycin or DMSO treated larval eyes at 2 and 4 days post injury(dpi). MTZ+ for ablated samples and MTZ- for unablated.