{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:47:00Z","timestamp":1790444820080,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301181"],"award-info":[{"award-number":["82301181"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.exer.2025.110777","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:16:01Z","timestamp":1764634561000},"page":"110777","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Tacrolimus exerts anti-inflammatory effects in moderate to severe dry eye through activation of autophagy-lysosomal pathway"],"prefix":"10.1016","volume":"263","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-5023","authenticated-orcid":false,"given":"Yunjing","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7646-2699","authenticated-orcid":false,"given":"Shaozhen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2025.110777_bib1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0190-9622(98)70541-9","article-title":"Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children","volume":"38","author":"Alaiti","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.exer.2025.110777_bib2","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1681\/ASN.2016111208","article-title":"Janus kinase 2 regulates transcription factor EB expression and autophagy completion in glomerular podocytes","volume":"28","author":"Alghamdi","year":"2017","journal-title":"JASN (J. Am. Soc. Nephrol.)"},{"key":"10.1016\/j.exer.2025.110777_bib3","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110777_bib4","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17128-0","article-title":"Elevation of autophagy markers in Sj\u00f6gren syndrome dry eye","volume":"7","author":"Byun","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2025.110777_bib5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/mi.2009.5","article-title":"IL-17 disrupts corneal barrier following desiccating stress","volume":"2","author":"De Paiva","year":"2009","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.exer.2025.110777_bib6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.exer.2025.110777_bib7","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.4049\/jimmunol.0801772","article-title":"Suppression of NF-kappaB by cyclosporin a and tacrolimus (FK506) via induction of the C\/EBP family: implication for unfolded protein response","volume":"182","author":"Du","year":"2009","journal-title":"J. Immunol."},{"key":"10.1016\/j.exer.2025.110777_bib8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4049\/jimmunol.137.1.245","article-title":"Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1)","volume":"137","author":"Dustin","year":"1986","journal-title":"J. Immunol."},{"key":"10.1016\/j.exer.2025.110777_bib9","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1101\/gad.213827.113","article-title":"A RANKL\u2013PKC\u03b2\u2013TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts","volume":"27","author":"Ferron","year":"2013","journal-title":"Genes Dev."},{"key":"10.1016\/j.exer.2025.110777_bib10","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1001\/archopht.1960.01840010538009","article-title":"Cell production and migration in the epithelial layer of the cornea","volume":"64","author":"Hanna","year":"1960","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.exer.2025.110777_bib11","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.66.2.5","article-title":"HMGB1 promotes lysosome-dependent cell death induced via dry eye by disrupting lysosomal homeostasis","volume":"66","author":"Hu","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2025.110777_bib12","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1167\/iovs.19-27872","article-title":"Changes in human tear proteome following topical treatment of dry eye disease: cyclosporine A versus diquafosol tetrasodium","volume":"60","author":"Ji","year":"2019","journal-title":"Investigative Opthalmol. Visual Sci."},{"key":"10.1016\/j.exer.2025.110777_bib13","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110777_bib14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jtos.2023.04.015","article-title":"Proteomic analysis of tears in dry eye disease: a prospective, double-blind multicenter study","volume":"29","author":"Jung","year":"2023","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110777_bib15","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1167\/iovs.19-27656","article-title":"Single-Cell RNA transcriptome helps define the limbal\/corneal epithelial stem\/early transit amplifying cells and how autophagy affects this population","volume":"60","author":"Kaplan","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2025.110777_bib16","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.7164\/antibiotics.40.1249","article-title":"FK-506, a novel immunosuppressant isolated from a streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics","volume":"40","author":"Kino","year":"1987","journal-title":"J. Antibiot. (Tokyo)"},{"key":"10.1016\/j.exer.2025.110777_bib17","first-page":"1","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy","volume":"vol. 12","author":"Klionsky","year":"2016"},{"key":"10.1016\/j.exer.2025.110777_bib18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1167\/iovs.13-12925","article-title":"Effect of 0.025% FK-506 eyedrops on botulinum toxin B-Induced mouse dry eye","volume":"56","author":"Lin","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2025.110777_bib19","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2147\/OPTH.S124889","article-title":"Impression cytology implicates cell autophagy in aqueous deficiency dry eye","volume":"11","author":"Lin","year":"2017","journal-title":"Clin. Ophthalmol."},{"key":"10.1016\/j.exer.2025.110777_bib20","article-title":"Topical corticosteroids for dry eye","volume":"2022","author":"Liu","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.exer.2025.110777_bib21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11010-020-03832-5","article-title":"Autophagy modulation in animal models of corneal diseases: a systematic review","volume":"474","author":"Mart\u00ednez-Chac\u00f3n","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.exer.2025.110777_bib22","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/ncb3114","article-title":"Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB","volume":"17","author":"Medina","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.exer.2025.110777_bib23","doi-asserted-by":"crossref","first-page":"11436","DOI":"10.1074\/jbc.M112.437103","article-title":"Deletion of autophagy-related 5 (Atg 5) and Pik3c3 genes in the lens causes cataract independent of programmed organelle degradation","volume":"288","author":"Morishita","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.exer.2025.110777_bib24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.clae.2015.04.004","article-title":"Treatment of Sj\u00f6gren\u2019s syndrome dry eye using 0.03% tacrolimus eye drop: prospective double-blind randomized study","volume":"38","author":"Moscovici","year":"2015","journal-title":"Contact Lens Anterior Eye"},{"key":"10.1016\/j.exer.2025.110777_bib25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1167\/iovs.61.10.31","article-title":"Autophagy in the aging and experimental ocular hypertensive mouse model","volume":"61","author":"Nettesheim","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2025.110777_bib26","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1093\/hmg\/ddr306","article-title":"Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways","volume":"20","author":"Palmieri","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2025.110777_bib27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1080\/15548627.2017.1287658","article-title":"Eyeing autophagy and macropinocytosis in the corneal\/limbal epithelia","volume":"13","author":"Peng","year":"2017","journal-title":"Autophagy"},{"key":"10.1016\/j.exer.2025.110777_bib28","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1016\/j.bbamcr.2014.09.015","article-title":"Decline in cellular clearance systems induces inflammasome signaling in human ARPE-19 cells","volume":"1843","author":"Piippo","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.exer.2025.110777_bib29","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201798804","article-title":"The complex relationship between TFEB transcription factor phosphorylation and subcellular localization","volume":"37","author":"Puertollano","year":"2018","journal-title":"EMBO J."},{"key":"10.1016\/j.exer.2025.110777_bib30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A gene network regulating lysosomal biogenesis and function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.exer.2025.110777_bib31","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB links autophagy to lysosomal biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.exer.2025.110777_bib32","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/emboj.2012.32","article-title":"A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB: self-regulation of the lysosome via mTOR and TFEB","volume":"31","author":"Settembre","year":"2012","journal-title":"EMBO J."},{"key":"10.1016\/j.exer.2025.110777_bib33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/sji.12398","article-title":"Different effects of tacrolimus on innate and adaptive immune cells in the allograft transplantation","volume":"83","author":"Shao","year":"2016","journal-title":"Scand. J. Immunol."},{"key":"10.1016\/j.exer.2025.110777_bib34","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1097\/ICO.0000000000002224","article-title":"Topical tacrolimus in Thygeson superficial punctate keratitis","volume":"39","author":"Shoughy","year":"2020","journal-title":"Cornea"},{"key":"10.1016\/j.exer.2025.110777_bib35","article-title":"TFOS DEWS III digest report","author":"Stapleton","year":"2025","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2025.110777_bib36","first-page":"584","volume":"vol. 17","author":"Thomson","year":"1995"},{"key":"10.1016\/j.exer.2025.110777_bib37","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1097\/ICL.0000000000000643","article-title":"A new perspective on dry eye classification: proposal by the Asia dry eye society","volume":"46","author":"Tsubota","year":"2020","journal-title":"Eye Contact Lens"},{"key":"10.1016\/j.exer.2025.110777_bib38","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/eye.2016.186","article-title":"Depression and anxiety in dry eye disease: a systematic review and meta-analysis","volume":"30","author":"Wan","year":"2016","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.exer.2025.110777_bib39","first-page":"1","article-title":"Autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory responses in AMD: from mechanisms to therapeutic potential","volume":"2019","author":"Wang","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.exer.2025.110777_bib40","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jtos.2017.03.006","article-title":"TFOS DEWS II tear film report","volume":"15","author":"Willcox","year":"2017","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110777_bib41","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jtos.2017.05.001","article-title":"TFOS DEWS II diagnostic methodology report","volume":"15","author":"Wolffsohn","year":"2017","journal-title":"Ocul. Surf."},{"key":"10.1016\/j.exer.2025.110777_bib42","article-title":"TFOS DEWS III diagnostic methodology","author":"Wolffsohn","year":"2025","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2025.110777_bib43","doi-asserted-by":"crossref","first-page":"144","DOI":"10.3390\/biology13030144","article-title":"The role of Insulin-like Growth Factor (IGF) System in the corneal epithelium homeostasis-from limbal epithelial stem cells to therapeutic applications","volume":"13","author":"Woronkowicz","year":"2024","journal-title":"Biology"},{"key":"10.1016\/j.exer.2025.110777_bib44","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1002\/ibd.21318","article-title":"Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis","volume":"16","author":"Yoshino","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"10.1016\/j.exer.2025.110777_bib45","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.3892\/mmr.2017.7353","article-title":"Tacrolimus downregulates inflammation by regulating pro-\/anti-inflammatory responses in LPS-induced keratitis","volume":"16","author":"Yu","year":"2017","journal-title":"Mol. Med. Rep."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483525005500?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483525005500?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:05:11Z","timestamp":1781323511000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483525005500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":45,"alternative-id":["S0014483525005500"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2025.110777","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tacrolimus exerts anti-inflammatory effects in moderate to severe dry eye through activation of autophagy-lysosomal pathway","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2025.110777","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"110777"}}