{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:11:16Z","timestamp":1790791876070,"version":"4.1.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Glaucoma UK"},{"name":"St Pauls Eye Appeal"},{"name":"GREAT Scholarships 2018\u2014China campaign"},{"name":"Republic of Turkey Ministry of National Education"},{"name":"MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership","award":["MR\/R015902\/1"],"award-info":[{"award-number":["MR\/R015902\/1"]}]},{"name":"Liverpool Research Eye Bank"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness, yet its underly mechanisms remain unclear. Elevated intraocular pressure (IOP), the only modifiable risk factor for POAG, arises from increased resistance to aqueous humor outflow within the conventional outflow pathway, which comprises the trabecular meshwork (TM) and the inner wall of Schlemm\u2019s canal. Dysfunction and cellular loss within this pathway, particularly in the TM, are consistent features of the disease; however, the mechanisms responsible for impaired tissue maintenance and regenerative failure remain unclear. TM progenitor cells (TMPCs) have the capacity to replace lost TM cells, suggesting that impaired progenitor function may contribute to disease progression. Transforming growth factor beta 2 (TGF\u03b22), which is consistently elevated in the aqueous humor of POAG patients, plays a key role in regulating stem cell differentiation. We proposed that excess TGF\u03b22 disrupts TMPC function, leading to progenitor depletion and TM dysfunction. Here, we show that TGF\u03b22 drives TMPCs toward a differentiated, fibrotic phenotype, increasing TM and profibrotic gene expression while reducing progenitor markers. These effects are mediated through TGF\u03b22\u2013SMAD2\/3 signaling, as inhibition of this pathway preserves TMPC characteristics and suppresses fibrotic gene induction. Our findings identify TGF\u03b22\u2013SMAD2\/3 signaling as a regulator of TMPC fate in vitro and suggest a potential mechanism by which elevated TGF\u03b22 may influence TMPC behavior under pathological conditions.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag033","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:43:05Z","timestamp":1779363785000},"source":"Crossref","is-referenced-by-count":2,"title":["Transforming growth factor beta-2 drives trabecular meshwork progenitor cell differentiation through SMAD2\/3 signaling"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-2846","authenticated-orcid":false,"given":"Xiaochen","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]},{"name":"Institute of Ophthalmology, University College London , London, EC1V 9EL,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine K","family":"Bilir","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]},{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia A","family":"Kingston","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria R","family":"Kearns","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1246-4166","authenticated-orcid":false,"given":"Colin E","family":"Willoughby","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United Kingdom"]},{"name":"Centre for Genomic Medicine, Biomedical Sciences Research Institute, Ulster University , Coleraine, BT52 1SA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl M","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, L69 3BX,","place":["United 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