Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells
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...
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| Format: | Article |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46428-z |
| _version_ | 1797259238724075520 |
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| author | Cheng Qian Ying Xin Cheng Qi Hui Wang Bryan C. Dong Donald J. Zack Seth Blackshaw Samer Hattar Feng-Quan Zhou Jiang Qian |
| author_facet | Cheng Qian Ying Xin Cheng Qi Hui Wang Bryan C. Dong Donald J. Zack Seth Blackshaw Samer Hattar Feng-Quan Zhou Jiang Qian |
| author_sort | Cheng Qian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T23:06:15Z |
| format | Article |
| id | doaj.art-b1cda4bead69404db2565077129f3d56 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:06:15Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b1cda4bead69404db2565077129f3d562024-03-17T12:30:01ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46428-zIntercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cellsCheng Qian0Ying Xin1Cheng Qi2Hui Wang3Bryan C. Dong4Donald J. Zack5Seth Blackshaw6Samer Hattar7Feng-Quan Zhou8Jiang Qian9Department of Orthopaedic Surgery, Johns Hopkins University School of MedicineDepartment of Ophthalmology, Johns Hopkins University School of MedicineDepartment of Orthopaedic Surgery, Johns Hopkins University School of MedicineSection on Light and Circadian Rhythms, National Institute of Mental HealthNeuroscience Study Program, Krieger School of Arts & Sciences, Johns Hopkins UniversityDepartment of Ophthalmology, Johns Hopkins University School of MedicineDepartment of Ophthalmology, Johns Hopkins University School of MedicineSection on Light and Circadian Rhythms, National Institute of Mental HealthDepartment of Orthopaedic Surgery, Johns Hopkins University School of MedicineDepartment of Ophthalmology, Johns Hopkins University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-024-46428-z |
| spellingShingle | Cheng Qian Ying Xin Cheng Qi Hui Wang Bryan C. Dong Donald J. Zack Seth Blackshaw Samer Hattar Feng-Quan Zhou Jiang Qian Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells Nature Communications |
| title | Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells |
| title_full | Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells |
| title_fullStr | Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells |
| title_full_unstemmed | Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells |
| title_short | Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells |
| title_sort | intercellular communication atlas reveals oprm1 as a neuroprotective factor for retinal ganglion cells |
| url | https://doi.org/10.1038/s41467-024-46428-z |
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