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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.<\/jats:p>","DOI":"10.1186\/s40478-025-01974-5","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T05:53:46Z","timestamp":1743832426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TRPA1 exacerbates selective retinal ganglion cell vulnerability under acute ocular hypertension"],"prefix":"10.1186","volume":"13","author":[{"given":"Wenhan","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yicong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghuai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"1974_CR1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.preteyeres.2016.12.003","volume":"57","author":"X Sun","year":"2017","unstructured":"Sun X et al (2017) Primary angle closure glaucoma: what we know and what we don\u2019t know. 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Biochemistry (Mosc) 84(2):101\u2013118","DOI":"10.1134\/S0006297919020020"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-025-01974-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-025-01974-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-025-01974-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T13:42:06Z","timestamp":1743860526000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-025-01974-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,5]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1974"],"URL":"https:\/\/doi.org\/10.1186\/s40478-025-01974-5","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,5]]},"assertion":[{"value":"16 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study adhered to the ARVO Statement for Use of Animals in Ophthalmic and Vision Research. Our research and animal experiments were approved by the Research Ethical Review Committee for Laboratory Animal Welfare of Fudan University and the Laboratory Animal Management and Ethic Committee of Eye & ENT Hospital of Fudan University, Shanghai of China.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}