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Publication : Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells.

First Author  Qian C Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  2206
PubMed ID  38467611 Mgi Jnum  J:376615
Mgi Id  MGI:8271053 Doi  10.1038/s41467-024-46428-z
Citation  Qian C, et al. (2024) Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells. Nat Commun 15(1):2206
abstractText  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 Muller 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 mu-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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