{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:11:56Z","timestamp":1783793516982,"version":"3.55.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>Tears are easy to collect, repeatable, and reflect the state of the corneal surface\u2014attributes that make them attractive for bedside monitoring after surgery or injury. We performed a cross-species meta-analysis of tear proteomes from patients undergoing photorefractive keratectomy (PRK) and from mice after mechanical epithelial abrasion to define molecular programs that are both conserved and clinically actionable. Roughly one-third of the injury response was shared between species, centering on innate immune activation (complement\/acute phase), epithelial migration and cytoskeletal remodeling, and a calibrated suppression of proteolysis. From this overlap we distilled a small, secreted tear panel that stages injury and early resolution in both species: transferrin and hemopexin (iron\/heme scavenging), albumin (vascular leak), apolipoprotein A-I (barrier lipid transport), and the coagulation modulators kininogen-1 and \u03b12-antiplasmin (protease\/fibrinolysis control). This panel rises at the first post-injury sampling (D0 in humans; 6\u201312\u00a0h in mice) and trends toward baseline during recovery (D3 in humans; \u223c24\u00a0h in mice), providing a practical kinetic signature for clinical decision-making. Standardized sampling at D0\/D3 can therefore quantify acute damage and early healing, enable pharmacodynamic readouts for anti-inflammatory or barrier-stabilizing therapies, and support risk stratification after epithelial procedures. Species-specific differences (human: secretory\/immune surveillance; mouse: mitochondrial\/metabolic reboot) clarify which preclinical signals are most likely to translate. Together, these findings establish a conserved tear blueprint of corneal repair and nominate a minimal, deployable biomarker set to accelerate clinical monitoring and therapeutic development in ocular surface disease.<\/jats:p>","DOI":"10.3389\/ebm.2025.10866","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:40:47Z","timestamp":1770039647000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated tear proteomics define the molecular blueprint of corneal epithelial repair"],"prefix":"10.3389","volume":"250","author":[{"given":"Nadege","family":"Feret","sequence":"first","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilou","family":"Decoudu","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Vialaret","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]},{"name":"IRMB-PPC, University Montpellier, CHU Montpellier, INSERM CNRS","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Hirtz","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]},{"name":"IRMB-PPC, University Montpellier, CHU Montpellier, INSERM CNRS","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Loulier","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Daien","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]},{"name":"Department of Ophthalmology, Gui de Chauliac Hospital","place":["Montpellier, France"]},{"name":"The Save Sight Institute, Sydney Medical School, The University of Sydney","place":["Sydney, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Michon","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier, University Montpellier, INSERM","place":["Montpellier, France"]},{"name":"Department of Ophthalmology, Gui de Chauliac Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology of the cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J Cataract Refract Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1002\/dvdy.24179","article-title":"The vertebrate corneal epithelium: from early specification to constant renewal","volume":"243","author":"Dhouailly","year":"2014","journal-title":"Dev Dyn Off Publ Am Assoc Anat"},{"key":"B3","doi-asserted-by":"publisher","first-page":"906155","DOI":"10.3389\/fphys.2022.906155","article-title":"Zebrafish cornea formation and homeostasis reveal a slow maturation process, similarly to terrestrial vertebrates\u2019 corneas","volume":"13","author":"Ikkala","year":"2022","journal-title":"Front Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/s1542-0124(12)70613-4","article-title":"Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology","volume":"5","author":"Klenkler","year":"2007","journal-title":"Ocul Surf"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exer.2013.10.008","article-title":"Complexity of the tear film: importance in homeostasis and dysfunction during disease","volume":"117","author":"Dartt","year":"2013","journal-title":"Exp Eye Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"Pflugfelder","year":"2020","journal-title":"Exp Eye Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"dev176693","DOI":"10.1242\/dev.176693","article-title":"Ectodysplasin-A signaling is a key integrator in the lacrimal gland\u2013cornea feedback loop","volume":"146","author":"Kuony","year":"2025","journal-title":"Development"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.4110\/in.2019.19.e3","article-title":"Age-related autoimmune changes in lacrimal glands","volume":"19","author":"de Souza","year":"2019","journal-title":"Immune Netw"},{"key":"B9","doi-asserted-by":"publisher","first-page":"108089","DOI":"10.1016\/j.exer.2020.108089","article-title":"Corneal wound healing","volume":"197","author":"Wilson","year":"2020","journal-title":"Exp Eye Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.preteyeres.2012.06.002","article-title":"Tear analysis in ocular surface diseases","volume":"31","author":"Zhou","year":"2012","journal-title":"Prog Retin Eye Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.exer.2013.07.015","article-title":"Tears as a source of biomarkers for ocular and systemic diseases","volume":"117","author":"von","year":"2013","journal-title":"Exp Eye Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13167-016-0065-3","article-title":"Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine","volume":"7","author":"Hagan","year":"2016","journal-title":"EPMA J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.jprot.2016.05.006","article-title":"Human tear proteomics and peptidomics in ophthalmology: toward the translation of proteomic biomarkers into clinical practice","volume":"150","author":"Azkargorta","year":"2017","journal-title":"J Proteomics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.17.665304","article-title":"Integrated tear proteomics define the molecular blueprint of corneal epithelial repair","author":"Feret","year":"2025"},{"key":"B15","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s11658-025-00804-9","article-title":"Decoding epithelial regeneration in the cornea: multi-omic analysis reveals cellular plasticity as central mechanism","volume":"30","author":"Feret","year":"2025","journal-title":"Cell Mol Biol Lett"},{"key":"B16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1167\/iovs.66.13.49","article-title":"Temporal analysis of tear fluid proteome reveals critical corneal repair events after photorefractive surgery","volume":"66","author":"Feret","year":"2025","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s13167-021-00265-y","article-title":"Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine","volume":"12","author":"Zhan","year":"2021","journal-title":"EPMA J"},{"key":"B18","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1002\/mas.21691","article-title":"Mass spectrometry-based tear proteomics for noninvasive biomarker discovery","volume":"41","author":"Ponzini","year":"2022","journal-title":"Mass Spectrom Rev"},{"key":"B19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/1873-3468.14964","article-title":"Keep calm and reboot - how cells restart transcription after DNA damage and DNA repair","volume":"599","author":"Donnio","year":"2025","journal-title":"FEBS Lett"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.3390\/ijms23042307","article-title":"Comparison of different mass spectrometry workflows for the proteomic analysis of tear fluid","volume":"23","author":"Jones","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B21","first-page":"456","article-title":"Investigation of the human tear film proteome using multiple proteomic approaches","volume":"14","author":"Green-Church","year":"2008","journal-title":"Mol Vis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2174\/156652406776894572","article-title":"Toll-like receptors and corneal innate immunity","volume":"6","author":"Kumar","year":"2006","journal-title":"Curr Mol Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.exer.2013.07.014","article-title":"Antimicrobial compounds in tears","volume":"117","author":"McDermott","year":"2013","journal-title":"Exp Eye Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1038\/s41385-022-00551-6","article-title":"Mucosal immunology of the ocular surface","volume":"15","author":"de Paiva","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"609","DOI":"10.20517\/evcna.2025.72","article-title":"Tear-derived extracellular vesicles as diagnostic biomarkers for ocular and neurodegenerative diseases: opportunities and challenges","volume":"6","author":"Sanroque-Mu\u00f1oz","year":"2025","journal-title":"Extracell Vesicles Circ Nucleic Acids"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1002\/1873-3468.70004","article-title":"The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond","volume":"599","author":"Fatima","year":"2025","journal-title":"FEBS Lett"},{"key":"B27","doi-asserted-by":"publisher","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 Retin Eye Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1016\/j.cmet.2021.07.017","article-title":"Metabolic orchestration of the wound healing response","volume":"33","author":"Eming","year":"2021","journal-title":"Cell Metab"},{"key":"B29","doi-asserted-by":"publisher","first-page":"103654","DOI":"10.1016\/j.ebiom.2021.103654","article-title":"Cisd2 plays an essential role in corneal epithelial regeneration","volume":"73","author":"Sun","year":"2021","journal-title":"EBioMedicine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.3390\/ijms26031290","article-title":"Disrupted mitochondrial dynamics impair corneal epithelial healing in neurotrophic keratopathy","volume":"26","author":"Jin","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/iovs.65.6.14","article-title":"Mitochondria transplantation promotes corneal epithelial wound healing","volume":"65","author":"Raz","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/imm.12716","article-title":"Mucosal immune tolerance at the ocular surface in health and disease","volume":"150","author":"Galletti","year":"2017","journal-title":"Immunology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213X-9-4","article-title":"Mosaic analysis of stem cell function and wound healing in the mouse corneal epithelium","volume":"9","author":"Mort","year":"2009","journal-title":"BMC Dev Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J Immunol Baltim Md"},{"key":"B35","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1615\/critrevimmunol.2014011600","article-title":"Differences in innate immune response between man and mouse","volume":"34","author":"Zschaler","year":"2014","journal-title":"Crit Rev Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"B37","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/prca.201400084","article-title":"Unraveling the molecular repertoire of tears as a source of biomarkers: beyond ocular diseases","volume":"9","author":"Pieragostino","year":"2015","journal-title":"Proteomics Clin Appl"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2025.10866\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:56:31Z","timestamp":1771995391000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/articles\/10.3389\/ebm.2025.10866\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":37,"alternative-id":["10.3389\/ebm.2025.10866"],"URL":"https:\/\/doi.org\/10.3389\/ebm.2025.10866","relation":{},"ISSN":["1535-3699"],"issn-type":[{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"article-number":"10866"}}