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Unfortunately, there is limited treatment for diabetes-induced corneal damage. The current project investigates a novel, peptide-based combination therapy, thymosin beta-4 and vasoactive intestinal peptide (T\u03b24\/VIP), against high-glucose-induced damage to the corneal epithelium. Electric cell\u2013substrate impedance sensing (ECIS) was used for real-time monitoring of barrier function and wound healing of human corneal epithelial cells maintained in either normal glucose (5 mM) or high glucose (25 mM) \u00b1 T\u03b24 (0.1%) and VIP (5 nM). Barrier integrity was assessed by resistance, impedance, and capacitance measurements. For the wound healing assay, cell migration was also monitored. Corneal epithelial tight junction proteins (ZO-1, ZO-2, occludin, and claudin-1) were assessed to confirm our findings. Barrier integrity and wound healing were significantly impaired under high-glucose conditions. However, barrier function and cell migration significantly improved with T\u03b24\/VIP treatment. These findings were supported by high-glucose-induced downregulation of tight junction proteins that were effectively maintained similar to normal levels when treated with T\u03b24\/VIP. These results strongly support the premise that T\u03b24 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage. In addition, this work highlights the potential for significant translational impact regarding the treatment of diabetic patients and associated complications of the cornea.<\/jats:p>","DOI":"10.3390\/bios13110974","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:25:31Z","timestamp":1699356331000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Novel Combination Therapy T\u03b24\/VIP Protects against Hyperglycemia-Induced Changes in Human Corneal Epithelial Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Abdul Shukkur","family":"Ebrahim","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Carion","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanzeela","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Win","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Kani","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Central Florida College of Health Professions and Sciences, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-7887","authenticated-orcid":false,"given":"Ashten","family":"Stambersky","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8480-6252","authenticated-orcid":false,"given":"Ahmed S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-7327","authenticated-orcid":false,"given":"Gabriel","family":"Sosne","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-1170","authenticated-orcid":false,"given":"Elizabeth A.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","first-page":"180","article-title":"Diabetic keratopathy","volume":"79","author":"Schultz","year":"1981","journal-title":"Trans. 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