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Myofibroblasts directly promote fibrosis by producing excessive extracellular matrix (ECM) proteins and alpha\u2010smooth muscle actin (\u0251\u2010SMA). In addition, macrophages have been shown to promote fibrosis by secreting pro\u2010fibrotic factors to stimulate myofibroblast formation. However, the capacity of macrophages to directly remodel ECM remains understudied. This study utilized a mouse model of corneal injury and fibrosis to determine whether macrophages transform into myofibroblast\u2010like cells during ocular surface inflammation. Following injury, F4\/80\u2009+\u2009\u0251\u2010SMA+ macrophages were present at the early stages of wound healing and increased in frequency and \u0251\u2010SMA intensity during the remodeling stage. The increase in F4\/80\u2009+\u2009\u0251\u2010SMA+ macrophages occurred due to the microenvironment transitioning from an inflammatory state to a pro\u2010fibrotic state. Activated human and mouse macrophages treated with pro\u2010fibrotic cytokines (IL\u201010 and TGF\u2010\u03b21) transitioned to \u0251\u2010SMA+ macrophages, adopting a spindle\u2010like phenotype and expressing signature myofibroblast ECM and cytoskeletal components, including \u0251\u2010SMA, desmin, fibronectin, and collagen III. Furthermore, gel contraction assays showed \u0251\u2010SMA+ macrophages significantly contracted a collagen gel, making them functionally resemble myofibroblasts. The results of this study indicate that macrophages have the capacity to transdifferentiate into myofibroblasts during ocular surface inflammation.<\/jats:p>","DOI":"10.1096\/fj.202403287rr","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:33:41Z","timestamp":1747992821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Macrophages Transdifferentiate Into Myofibroblasts During Ocular Surface Inflammation"],"prefix":"10.1096","volume":"39","author":[{"given":"Nishant R.","family":"Sinha","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay K.","family":"Pulimamidi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School Schepens Eye 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