神经保护
神经科学
视网膜神经节细胞
视网膜
视网膜
细胞内
生物
细胞生物学
生物化学
作者
Qian Cheng,Ying Xin,Cheng Qi,Hui Wang,Bryan Dong,Donald J. Zack,Seth Blackshaw,Samer Hattar,Feng‐Quan Zhou,Jiang Qian
标识
DOI:10.1038/s41467-024-46428-z
摘要
Abstract Previous studies of neuronal survival have primarily focused on identifying intrinsic mechanisms controlling the process. This study explored how intercellular communication contributes to retinal ganglion cell (RGC) survival following optic nerve crush based on single-cell RNA-seq analysis. We observed transcriptomic changes in retinal cells in response to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing RGC subclasses characterized by distinct resilience to cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with neighboring cells. We identified 47 interactions stronger in high-survival RGCs, likely mediating neuroprotective effects. We validated one identified target, the μ-opioid receptor (Oprm1), to be neuroprotective in three retinal injury models. Although the endogenous Oprm1 is preferentially expressed in intrinsically photosensitive RGCs, its neuroprotective effect can be transferred to other subclasses by pan-RGC overexpression of Oprm1. Lastly, manipulating the Oprm1 activity improved visual functions in mice.
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