{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:18:42Z","timestamp":1781115522225,"version":"3.54.1"},"reference-count":76,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["#R01EY030576"],"award-info":[{"award-number":["#R01EY030576"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Veterans Administration","award":["#I01BX005055"],"award-info":[{"award-number":["#I01BX005055"]}]},{"name":"VA Research Career Scientist","award":["#IK6BX005691"],"award-info":[{"award-number":["#IK6BX005691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Corneal problems, such as delayed and incomplete wound repair, are frequent in diabetes, affecting up to 70% of diabetic patients. In skin, histone deacetylases (HDACs) have been previously found to repress expression of the glycerol channel aquaporin-3 (AQP3), the deficiency of which delays corneal wound healing. We hypothesized that the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) would improve corneal healing in diabetic mice. Diabetic and normoglycemic C57BL\/6J male and female mice were subjected to corneal debridement. Wounds were treated topically with vehicle or SAHA every four hours until they healed. Treatment with SAHA improved wound healing in both normoglycemic and hyperglycemic male mice but, unexpectedly, no changes were detected in female mice. In male mice interleukin-1beta (IL-1\u03b2) and tumor necrosis factor (TNF) were significantly increased in diabetic corneas, and SAHA reduced their expression, returning IL-1\u03b2 and TNF to levels comparable to those in normoglycemic mice regardless of treatment. In normoglycemic male mice, AQP3 levels were not changed in the cornea with SAHA treatment but the expression of AQP3 was increased in the wound\u2019s edge relative to the rest of the cornea. In vitro SAHA treatment of human corneal epithelial cells (HCECs) significantly increased protein expression of AQP3, important for corneal wound healing, but had no effect on ROS production. In conclusion, treatment with SAHA improved corneal wound healing, not only in male mice with diabetes and delayed wound healing but also in normoglycemic male mice; therefore, SAHA could potentially be repurposed as a topical treatment clinically to improve corneal wound healing.<\/jats:p>","DOI":"10.3390\/cells14231880","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T11:50:13Z","timestamp":1764244213000},"page":"1880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histone Deacetylase Inhibition Enhances AQP3 Levels in Human Corneal Epithelial Cells and Corneal Wound Healing in Normoglycemic and Diabetic Male Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Samuel","family":"Melnyk","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ronderos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3664-5025","authenticated-orcid":false,"given":"Vivek","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-4522","authenticated-orcid":false,"given":"Maribeth H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-9887","authenticated-orcid":false,"given":"Mitchell A.","family":"Watsky","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3146-162X","authenticated-orcid":false,"given":"Wendy B.","family":"Bollag","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"},{"name":"James and Jean Culver Vision Discovery Institute, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA"},{"name":"VA Augusta Health Care System, Augusta, GA 30904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.ophtha.2009.01.002","article-title":"In vivo confocal microscopic findings of corneal wound healing after corneal epithelial debridement in diabetic vitrectomy","volume":"116","author":"Chen","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.visres.2017.03.002","article-title":"Diabetic complications in the cornea","volume":"139","author":"Ljubimov","year":"2017","journal-title":"Vis. 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