TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension
Abstract Acute ocular hypertension (AOH), a major cause of progressive irreversible vision loss, showed significant retinal ganglion cell (RGC) degeneration as well as selective RGC vulnerability upon functional tests, yet the underlyding mechanisms remain incompletely understood. Here, we report th...
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BMC
2025-04-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-025-01974-5 |
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| author | Wenhan Lu Yu Wang Wei Hu Xinyi Lin Xiaoyu Tong Yi Tian Yuning Chen Yicong Wang Yan Xiao Hongfang Yang Yi Feng Xinghuai Sun |
| author_facet | Wenhan Lu Yu Wang Wei Hu Xinyi Lin Xiaoyu Tong Yi Tian Yuning Chen Yicong Wang Yan Xiao Hongfang Yang Yi Feng Xinghuai Sun |
| author_sort | Wenhan Lu |
| collection | DOAJ |
| description | Abstract Acute ocular hypertension (AOH), a major cause of progressive irreversible vision loss, showed significant retinal ganglion cell (RGC) degeneration as well as selective RGC vulnerability upon functional tests, yet the underlyding mechanisms remain incompletely understood. Here, we report the activation of transient receptor potential ankyrin 1 (TRPA1), a mechanosensitive ion channel on RGCs under AOH by RT-qPCR, Western blot, immunofluorescent, flow cytometry and calcium imaging tests. Downstream CaMKII/CREB pathways were evaluated, showing significantly elevated phospho-CaMKII and down-regulated phospho-CREB1 under AOH. Further, by applying a modified whole-brain clearing method, the region-specific RGC axonal damage among lateral geniculate nuclei (LGN) subregions were adopted to detect the involvement of TRPA1 on selective RGC vulnerability. Together with tissue-specific knock-out or channel inhibition test, the exacerbation of TRPA1 on RGC degeneration as well as selective injury tendency under AOH was confirmed. In virtue of our modified whole-brain clearing method, our data confirmed the innovational method to study the mechanisms behind selective vulnerability of neuronal cells, and in the meantime revealed the potential therapeutic opportunity of targeting TRPA1 for patients suffering from AOH attack. |
| format | Article |
| id | doaj-art-a03adbb0cfb94dd2a3f306280b94280a |
| institution | OA Journals |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-a03adbb0cfb94dd2a3f306280b94280a2025-08-20T02:25:41ZengBMCActa Neuropathologica Communications2051-59602025-04-0113112010.1186/s40478-025-01974-5TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertensionWenhan Lu0Yu Wang1Wei Hu2Xinyi Lin3Xiaoyu Tong4Yi Tian5Yuning Chen6Yicong Wang7Yan Xiao8Hongfang Yang9Yi Feng10Xinghuai Sun11Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan UniversityReproductive Medicine Center, Zhongshan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan UniversityDepartment of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan UniversityAbstract Acute ocular hypertension (AOH), a major cause of progressive irreversible vision loss, showed significant retinal ganglion cell (RGC) degeneration as well as selective RGC vulnerability upon functional tests, yet the underlyding mechanisms remain incompletely understood. Here, we report the activation of transient receptor potential ankyrin 1 (TRPA1), a mechanosensitive ion channel on RGCs under AOH by RT-qPCR, Western blot, immunofluorescent, flow cytometry and calcium imaging tests. Downstream CaMKII/CREB pathways were evaluated, showing significantly elevated phospho-CaMKII and down-regulated phospho-CREB1 under AOH. Further, by applying a modified whole-brain clearing method, the region-specific RGC axonal damage among lateral geniculate nuclei (LGN) subregions were adopted to detect the involvement of TRPA1 on selective RGC vulnerability. Together with tissue-specific knock-out or channel inhibition test, the exacerbation of TRPA1 on RGC degeneration as well as selective injury tendency under AOH was confirmed. In virtue of our modified whole-brain clearing method, our data confirmed the innovational method to study the mechanisms behind selective vulnerability of neuronal cells, and in the meantime revealed the potential therapeutic opportunity of targeting TRPA1 for patients suffering from AOH attack.https://doi.org/10.1186/s40478-025-01974-5TRPA1Acute ocular hypertensionRGC central projectionNeuronal selective vulnerabilityTissue optical clearing |
| spellingShingle | Wenhan Lu Yu Wang Wei Hu Xinyi Lin Xiaoyu Tong Yi Tian Yuning Chen Yicong Wang Yan Xiao Hongfang Yang Yi Feng Xinghuai Sun TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension Acta Neuropathologica Communications TRPA1 Acute ocular hypertension RGC central projection Neuronal selective vulnerability Tissue optical clearing |
| title | TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| title_full | TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| title_fullStr | TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| title_full_unstemmed | TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| title_short | TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| title_sort | trpa1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension |
| topic | TRPA1 Acute ocular hypertension RGC central projection Neuronal selective vulnerability Tissue optical clearing |
| url | https://doi.org/10.1186/s40478-025-01974-5 |
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