{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:56:07Z","timestamp":1789707367323,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sunnybrook Foundation and Fighting Blindness Canada"},{"name":"Vision Sciences Research Program Ontario Student Opportunity Trust Fund (VSRP OSOTF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by corneal endothelial cell (CEC) loss and guttae formation. Elevated levels of Transforming Growth Factor-Beta 1 and 2 (TGF-\u03b21\/-\u03b22) have been reported in the aqueous humor (AH) of FECD patients and have been implicated with abnormal extracellular matrix (ECM) production, endothelial-to-mesenchymal transition (EndoMT), the unfolded protein response, and cell death. However, how TGF-\u03b2 signaling affects cell migration in FECD remains to be elucidated. In this study, we found that TGF-\u03b22 levels were significantly elevated in the AH of FECD patients compared to controls. We performed bulk RNA sequencing on FECD CECs treated with TGF-\u03b21 or TGF-\u03b22 and identified the epithelial-to-mesenchymal (EMT) pathway as one of the top dysregulated pathways. We found that TGF-\u03b21 and TGF-\u03b22 increased EMT markers, filamentous-actin (F-actin) expression and produced more EMT-like phenotype in FECD and control CECs. We also observed that TGF-\u03b21 and TGF-\u03b22 significantly increased FECD CEC migration speed as detected by scratch assay and individual cell tracking and promoted individual cellular migration behavior. This study provides novel insight into FECD pathogenesis and how increased TGF-\u03b2 signaling promotes EndoMT and alters cellular migration in FECD CECs.<\/jats:p>","DOI":"10.3390\/ijms26146685","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T15:19:31Z","timestamp":1752247171000},"page":"6685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TGF-\u03b2 Promotes Endothelial-to-Mesenchymal Transition and Alters Corneal Endothelial Cell Migration in Fuchs Endothelial Corneal Dystrophy"],"prefix":"10.3390","volume":"26","author":[{"given":"Judy","family":"Yan","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1301-5984","authenticated-orcid":false,"given":"Brooke","family":"Lim","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisa","family":"Dhupar","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrine","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[{"name":"Kensington Eye Institute, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Moloney","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Sciences, University of British Colombia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-1490","authenticated-orcid":false,"given":"Stephan","family":"Ong Tone","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada"},{"name":"Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/jamaophthalmol.2015.4776","article-title":"Global Survey of Corneal Transplantation and Eye Banking","volume":"134","author":"Gain","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100863","DOI":"10.1016\/j.preteyeres.2020.100863","article-title":"Fuchs Endothelial Corneal Dystrophy: The Vicious Cycle of Fuchs Pathogenesis","volume":"80","author":"Kocaba","year":"2021","journal-title":"Prog. 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