Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion
Abstract Retinal ischemia/reperfusion (I/R) injury drives progressive retinal ganglion cell (RGC) loss, yet mechanisms underlying neuronal type-specific vulnerability remain unclear. Using a mouse model of bilateral common carotid artery ligation, we observe decreased vessel density in the inner ret...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08314-2 |
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| author | Meizhen Zhu Yuqing Wu Hang Gao Fujian Qi Xiaoyu Zhang Yanli Ran |
| author_facet | Meizhen Zhu Yuqing Wu Hang Gao Fujian Qi Xiaoyu Zhang Yanli Ran |
| author_sort | Meizhen Zhu |
| collection | DOAJ |
| description | Abstract Retinal ischemia/reperfusion (I/R) injury drives progressive retinal ganglion cell (RGC) loss, yet mechanisms underlying neuronal type-specific vulnerability remain unclear. Using a mouse model of bilateral common carotid artery ligation, we observe decreased vessel density in the inner retina following I/R. Here, the total RGCs exhibit much more cell loss than the intrinsic photosensitive RGCs (ipRGCs). This disparity is parallel with their different mTOR activity: for ipRGCs, the mTOR activity is much higher than the total RGCs both before and after I/R. Pharmacological experiments reveal that, mTOR activation in total RGCs and high mTOR activity maintenance in ipRGCs promote rapamycin to protect the total RGCs and ipRGCs against I/R injury, respectively. Notably, the protective effects of rapamycin on total RGCs and ipRGCs manifest under different light conditions. Our findings bridge the type-specific mTOR regulation in RGCs and their distinct susceptibility to I/R injury, which offers new insights into further targeted neuroprotection. |
| format | Article |
| id | doaj-art-c20b6a3ad3da4b639b8b2c0f4947d511 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c20b6a3ad3da4b639b8b2c0f4947d5112025-08-20T02:07:45ZengNature PortfolioCommunications Biology2399-36422025-06-018111410.1038/s42003-025-08314-2Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusionMeizhen Zhu0Yuqing Wu1Hang Gao2Fujian Qi3Xiaoyu Zhang4Yanli Ran5Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou UniversityKey Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou UniversityKey Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou UniversitySchool of Life Sciences, Lanzhou UniversityKey Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou UniversityKey Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou UniversityAbstract Retinal ischemia/reperfusion (I/R) injury drives progressive retinal ganglion cell (RGC) loss, yet mechanisms underlying neuronal type-specific vulnerability remain unclear. Using a mouse model of bilateral common carotid artery ligation, we observe decreased vessel density in the inner retina following I/R. Here, the total RGCs exhibit much more cell loss than the intrinsic photosensitive RGCs (ipRGCs). This disparity is parallel with their different mTOR activity: for ipRGCs, the mTOR activity is much higher than the total RGCs both before and after I/R. Pharmacological experiments reveal that, mTOR activation in total RGCs and high mTOR activity maintenance in ipRGCs promote rapamycin to protect the total RGCs and ipRGCs against I/R injury, respectively. Notably, the protective effects of rapamycin on total RGCs and ipRGCs manifest under different light conditions. Our findings bridge the type-specific mTOR regulation in RGCs and their distinct susceptibility to I/R injury, which offers new insights into further targeted neuroprotection.https://doi.org/10.1038/s42003-025-08314-2 |
| spellingShingle | Meizhen Zhu Yuqing Wu Hang Gao Fujian Qi Xiaoyu Zhang Yanli Ran Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion Communications Biology |
| title | Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion |
| title_full | Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion |
| title_fullStr | Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion |
| title_full_unstemmed | Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion |
| title_short | Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion |
| title_sort | differential regulation of mtor activity in retinal ganglion cells underlies their distinct susceptibility to ischemia reperfusion |
| url | https://doi.org/10.1038/s42003-025-08314-2 |
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