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

Author

Listed:
  • 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
    Johns Hopkins University School of Medicine)

  • Samer Hattar

    (National Institute of Mental Health)

  • Feng-Quan Zhou

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Zhejiang University School of Medicine)

  • Jiang Qian

    (Johns Hopkins University School of Medicine)

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.

Suggested Citation

  • Cheng Qian & Ying Xin & Cheng Qi & Hui Wang & Bryan C. Dong & Donald J. Zack & Seth Blackshaw & Samer Hattar & Feng-Quan Zhou & Jiang Qian, 2024. "Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46428-z
    DOI: 10.1038/s41467-024-46428-z
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    1. Ali D. Güler & Jennifer L. Ecker & Gurprit S. Lall & Shafiqul Haq & Cara M. Altimus & Hsi-Wen Liao & Alun R. Barnard & Hugh Cahill & Tudor C. Badea & Haiqing Zhao & Mark W. Hankins & David M. Berson &, 2008. "Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision," Nature, Nature, vol. 453(7191), pages 102-105, May.
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