Universität zu Köln

Volatier, Thomas ORCID: 0000-0002-3519-1359, Mourier, Andreas, Mann, Johanna ORCID: 0009-0006-7380-0916, Meshko, Berbang ORCID: 0009-0007-3646-3823, Hadrian, Karina ORCID: 0000-0001-9713-1477, Cursiefen, Claus ORCID: 0000-0002-1958-411X and Notara, Maria ORCID: 0000-0002-4243-1111 (2025). Characterization of Corneal Defects in ATG7-Deficient Mice. International Journal of Molecular Sciences, 26 (20). MDPI. ISSN 1422-0067

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Abstract

[Artikel-Nr. 9989] 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+/−), 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Volatier, Thomas UNSPECIFIED https://orcid.org/0000-0002-3519-1359 UNSPECIFIED Mourier, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mann, Johanna UNSPECIFIED https://orcid.org/0009-0006-7380-0916 UNSPECIFIED Meshko, Berbang UNSPECIFIED https://orcid.org/0009-0007-3646-3823 UNSPECIFIED Hadrian, Karina UNSPECIFIED https://orcid.org/0000-0001-9713-1477 UNSPECIFIED Cursiefen, Claus UNSPECIFIED https://orcid.org/0000-0002-1958-411X UNSPECIFIED Notara, Maria UNSPECIFIED https://orcid.org/0000-0002-4243-1111 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-800776
Identification Number:	10.3390/ijms26209989
Journal or Publication Title:	International Journal of Molecular Sciences
Volume:	26
Number:	20
Number of Pages:	21
Date:	14 October 2025
Publisher:	MDPI
ISSN:	1422-0067
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language cornea ; autophagy ; corneal epithelium ; ATG7 ; corneal homeostasis English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80077