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To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho\u2010associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy\u2010demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti\u2010glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP\u2010activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.<\/jats:p>","DOI":"10.1096\/fj.202101442rr","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T04:54:54Z","timestamp":1654491294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of Rho\u2010associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-0348","authenticated-orcid":false,"given":"Wei\u2010Ting","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Far Eastern Memorial Hospital  New Taipei City Taiwan"},{"name":"School of Medicine National Yang Ming Chiao Tung University  Hsinchu 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