{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:48:50Z","timestamp":1761007730614,"version":"build-2065373602"},"reference-count":86,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1607","FOR2240"],"award-info":[{"award-number":["SFB1607","FOR2240"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CMMC","award":["FP2020\/2022 A09"],"award-info":[{"award-number":["FP2020\/2022 A09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Regulated proteolysis via autophagy is essential for cellular homeostasis, yet the specific role of autophagy-related gene 7 (ATG7) in corneal epithelial maintenance remains unclear. Using a conditional knockout mouse model (Atg7f\/f K14Cre+\/\u2212), we investigated the impact of ATG7 deficiency on corneal epithelial autophagy, morphology, and vascular dynamics. Loss of ATG7 disrupted autophagosome formation, evidenced by increased LC3B expression but reduced LC3B-positive puncta and absence of autophagosomes ultrastructurally. Although gross corneal morphology was preserved, ATG7 deficiency led to thickened epithelium and increased peripheral lymphatic vessel sprouting, indicating a pro-inflammatory and pro-lymphangiogenic microenvironment. Proteomic analysis revealed upregulation of RAB8, TM9S3, and RETR3, suggesting activation of compensatory pathways such as exophagy, reticulophagy, and Golgiphagy. Inflammatory and angiogenic components were downregulated, suggesting a moderate loss of inhibitory capacity based on the lymphatic phenotypes observed. At the same time, while these two compensatory changes occur, other proteins that positively regulate lysosome formation are reduced, resulting in a phenotype linked to deficient autophagy. These findings demonstrate that ATG7-mediated autophagy maintains corneal epithelial homeostasis and immune privilege, with implications for understanding corneal inflammation and lymphangiogenesis in ocular surface diseases.<\/jats:p>","DOI":"10.3390\/ijms26209989","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"9989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Corneal Defects in ATG7-Deficient Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-1359","authenticated-orcid":false,"given":"Thomas","family":"Volatier","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Mourier","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7380-0916","authenticated-orcid":false,"given":"Johanna","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3646-3823","authenticated-orcid":false,"given":"Berbang","family":"Meshko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Hadrian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-411X","authenticated-orcid":false,"given":"Claus","family":"Cursiefen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"},{"name":"Cluster of Excellence for Aging Research (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Notara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"},{"name":"Cluster of Excellence for Aging Research (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 K\u00f6ln, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The ubiquitin system","volume":"67","author":"Hershko","year":"1998","journal-title":"Annu. 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