{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:13:07Z","timestamp":1790885587005,"version":"4.1.0"},"reference-count":584,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008993","name":"University of Zagreb","doi-asserted-by":"publisher","award":["10106-22-3071"],"award-info":[{"award-number":["10106-22-3071"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>To better address the challenge of corneal ulcer healing, with already available standard agents, and those recently introduced, such as stable gastric pentadecapeptide BPC 157, we introduced a novel conceptual framework\u2014the \u201ctriad\u201d of corneal ulcer healing\u2194corneal neovascularization\u2194intraocular pressure\u2014and extended it to avascular tissues such as tendon. Within this framework, cytoprotection serves as the unifying principle, underscoring that therapeutic effects are not isolated but interconnected. Preclinical studies with BPC 157 therapy, as a cytoprotection agent, illustrate this integration. BPC 157 rapidly normalizes elevated intraocular pressure in glaucomatous rats, preserves retinal integrity, restores pupil function, maintains corneal transparency during ulcer or abrasion healing, and counteracts both corneal neovascularization and dry eye. In parallel, its consistent efficacy in tendon injury models highlights a cytoprotective specificity across avascular tissues. The cornea\u2019s \u201cangiogenic privilege,\u201d preserved during healing and tendon recovery together, provides strong proof of concept. Furthermore, mapping standard therapeutic agents used for corneal ulcers, neovascularization, or glaucoma onto this triad, and linking them with tendon healing, reveals both shared pathways and inconsistencies across existing drug classes. Analyzed were the ascorbate, fibronectin, hyaluronic acid, metalloproteinase inhibitors, EGF, FGF, NGF, insulin, and IGF-1 (corneal ulcer healing), the antiangiogenic agents (endostatin, PAI-1, PEDF, angiostatin, TSP-1, TSP-2, IFN-\u03b1), corticosteroids, NSAIDs, cyclosporine A, anti-VEGF drops (treatment of corneal neovascularization), and alpha 2-agonists, beta-blockers, carboanhydrase inhibitors, muscarinic agonists, Rho-kinase inhibitors, and prostaglandin analogs (glaucoma). Taken together, these findings advance cytoprotection as a unifying therapeutic paradigm, with BPC 157 emerging as its first exemplar, and encourage further translational research toward clinical application.<\/jats:p>","DOI":"10.3390\/ph18121822","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"1822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Challenge of Corneal Ulcer Healing: A Novel Conceptual Framework, the \u201cTriad\u201d of Corneal Ulcer Healing\/Corneal Neovascularization\/Intraocular Pressure, and Avascular Tendon Healing, for Evaluation of Corneal Ulcer Therapy, Therapy of Neovascularization, Glaucoma Therapy, and Pentadecapeptide BPC 157 Efficacy"],"prefix":"10.3390","volume":"18","author":[{"given":"Sanja","family":"Masnec","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Ophthalmology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4836-7536","authenticated-orcid":false,"given":"Antonio","family":"Kokot","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience, School of Medicine Osijek, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3880-507X","authenticated-orcid":false,"given":"Tamara","family":"Kralj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Zlatar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0928-7952","authenticated-orcid":false,"given":"Kristina","family":"Loncaric","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9203-9732","authenticated-orcid":false,"given":"Marko","family":"Sablic","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience, School of Medicine Osijek, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miro","family":"Kalauz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Beslic","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Oroz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-6090","authenticated-orcid":false,"given":"Bozana","family":"Mrvelj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidija","family":"Beketic Oreskovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Oreskovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Strbe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Staresinic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-739X","authenticated-orcid":false,"given":"Goran","family":"Slivsek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alenka","family":"Boban Blagaic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-419X","authenticated-orcid":false,"given":"Sven","family":"Seiwerth","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-7283","authenticated-orcid":false,"given":"Anita","family":"Skrtic","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2252","authenticated-orcid":false,"given":"Predrag","family":"Sikiric","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.preteyeres.2015.07.002","article-title":"Progress in corneal wound healing","volume":"49","author":"Ljubimov","year":"2015","journal-title":"Prog. 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