{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:57:48Z","timestamp":1789109868559,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M722463"],"award-info":[{"award-number":["2022M722463"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271088"],"award-info":[{"award-number":["82271088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFB053"],"award-info":[{"award-number":["2023AFB053"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The oxidative stress\u2010induced premature senescence of trabecular meshwork (TM) represents a pivotal risk factor for the development of glucocorticoid\u2010induced glaucoma (GIG). This study aimed to elucidate the pathogenesis of TM senescence in GIG. MethodsIntraocular pressure (IOP), transmission electron microscopy and senescence\u2010associated protein expression in TM were evaluated in GIG mice. Protein expression of phosphoinositide\u20103\u2010kinase regulatory subunit 1 (PIK3R1) and monoamine oxidase A (MAOA), phosphorylation of AKT were quantified. ROS and mitochondrial superoxide levels were measured to evaluate cellular oxidative stress. Cell cycle analysis, \u03b2\u2010galactosidase staining, senescence\u2010associated protein expression were employed to assess the aging status of primary human trabecular meshwork cells (pHTMs). ResultsmRNA\u2010seq and KEGG analysis indicating PI3K\/AKT pathway as a key regulator in TM of GIG. PI3K inhibitor significantly prevented IOP elevation and abnormal mitochondrial morphology of TM in the GIG mouse model. PI3K inhibitor or selective silencing of <jats:italic>PIK3R1<\/jats:italic> alleviated dexamethasone (DEX)\u2010induced oxidative stress, also mitochondrial dysfunction, inhibiting MAOA expression in pHTMs. The same phenomenon was observed in the GIG models with inhibition of MAOA. Further KEGG analysis indicates that cellular senescence is the key factor in the pathogenesis of GIG. TM senescence was observed in both GIG mouse and cell models. Inhibition of the PI3K\/AKT\/MAOA pathway significantly alleviated DEX\u2010induced premature cellular senescence of TM in GIG models. Glucocorticoids activated the PI3K\/AKT\/MAOA pathway, leading to mitochondrial dysfunction, oxidative stress, and premature aging in TM, elevating IOP. This mechanism could be associated with the onset and progression of GIG, providing a potential approach for its treatment.<\/jats:p>","DOI":"10.1111\/acel.14452","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T12:33:46Z","timestamp":1734438826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Role of <scp>PI3K<\/scp>\/<scp>AKT<\/scp>\/<scp>MAOA<\/scp> in glucocorticoid\u2010induced oxidative stress and associated premature senescence of the trabecular meshwork"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5248-2708","authenticated-orcid":false,"given":"Pengyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Zhongnan Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7929"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(87)90593-5"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2016.01.062"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1137050"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddiscovery.2017.60"},{"key":"e_1_2_13_7_1","first-page":"1","article-title":"Mitophagy and oxidative stress: The role of aging","volume":"10","author":"De Gaetano A.","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0502"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00314-w"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-023-00977-4"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1083130"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.10.38"},{"key":"e_1_2_13_13_1","first-page":"237","article-title":"Genomic\/proteomic analyses of dexamethasone\u2010treated human trabecular meshwork cells reveal a role for GULP1 and ABR in phagocytosis","volume":"25","author":"Faralli J. 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