{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:22:19Z","timestamp":1760059339618,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet\u2019s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman\u2019s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea\u2019s 5-layer structure. IF examinations revealed that vimentin+ and \u03b1-smooth muscle actin (\u03b1SMA)+ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen+ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling.<\/jats:p>","DOI":"10.3390\/life15060939","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T08:18:06Z","timestamp":1749629886000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Healed Perforated Corneal Ulcers in Human"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-6690","authenticated-orcid":false,"given":"Yasser Helmy","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao","family":"Kusano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8131, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-9458","authenticated-orcid":false,"given":"Akio","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bukowiecki, A., Hos, D., Cursiefen, C., and Eming, S.A. 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