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

Cheng Qian, Ying Xin, Cheng Qi, Hui Wang, Bryan C. Dong, Donald J. Zack, Seth Blackshaw, Samer Hattar, Feng-Quan Zhou () and Jiang Qian ()
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Cheng Qian: Johns Hopkins University School of Medicine
Ying Xin: Johns Hopkins University School of Medicine
Cheng Qi: Johns Hopkins University School of Medicine
Hui Wang: National Institute of Mental Health
Bryan C. Dong: Johns Hopkins University
Donald J. Zack: Johns Hopkins University School of Medicine
Seth Blackshaw: Johns Hopkins University School of Medicine
Samer Hattar: National Institute of Mental Health
Feng-Quan Zhou: Johns Hopkins University School of Medicine
Jiang Qian: Johns Hopkins University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46428-z

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