Cannabinoid signaling promotes the reprogramming of Muller glia into proliferating progenitor cells.

摘要: Endocannabinoids (eCB) are lipid-based neurotransmitters that known to influence synaptic function in the visual system. eCBs also suppress neuroinflammation different pathological states. However, nothing is about roles of eCB system during reprogramming Muller glia (MG) into proliferating progenitor-like cells retina. Accordingly, we used chick and mouse model characterize expression patterns eCB-related genes applied pharmacological agents examine how impacts glial reactivity capacity MG become glia-derived progenitor (MGPCs). We probed single cell RNA-seq libraries identify with dynamic damaged retinas. inner retinal neurons expressed receptor CNR1, as well enzymes involved metabolism. In chick, intraocular injections 2-Arachidonoylglycerol (2-AG) Anandamide (AEA) potentiated formation MGPCs. Consistent these findings, CNR1-agonists MGLL-inhibitor promoted reprogramming, whereas CNR1-antagonist inhibitors synthesis suppressed reprogramming. Surprisingly, microglia were largely unaffected by increases or decreases signaling both models. eCB-signaling activation NFkB-reporter conclude retina influences important for regulating MGPCs, but not immune Main PointsMuller express CNR1 endocannabinoid genes. after damage promote derived chick. reduce NFkB activity glia.