{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:14:11Z","timestamp":1792196051985,"version":"4.4.0"},"reference-count":55,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2025,1,10]]},"DOI":"10.1167\/iovs.66.1.24","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T10:30:55Z","timestamp":1736505055000},"page":"24","source":"Crossref","is-referenced-by-count":7,"title":["Caspase 3\/GSDME-Mediated Corneal Epithelial Pyroptosis Promotes Dry Eye Disease"],"prefix":"10.1167","volume":"66","author":[{"given":"Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First People's Hospital of Xianyang City, Xianyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Hua","sequence":"additional","affiliation":[{"name":"Aier Eye Institute, Changsha, China"},{"name":"Tianjin Aier Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"9271","DOI":"10.3390\/ijms21239271","article-title":"Defining dry eye from a clinical perspective","volume":"21","author":"Tsubota","year":"2020","journal-title":"Int J Mol Sci"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.jtos.2017.08.003","article-title":"TFOS DEWS II Report Executive Summary","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II Epidemiology Report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"key":"bib4","doi-asserted-by":"publisher","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":"bib5","doi-asserted-by":"publisher","first-page":"4753","DOI":"10.1167\/iovs.03-0270","article-title":"The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity","volume":"44","author":"Begley","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jtos.2016.09.003","article-title":"New perspectives on dry eye definition and diagnosis: a consensus report by the Asia Dry Eye Society","volume":"15","author":"Tsubota","year":"2017","journal-title":"Ocul Surf"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: gasdermin-mediated programmed necrotic cell death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem Sci"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/imr.12287","article-title":"Pyroptotic cell death defends against intracellular pathogens","volume":"265","author":"Jorgensen","year":"2015","journal-title":"Immunol Rev"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jtos.2020.07.001","article-title":"NLRP12- and NLRC4-mediated corneal epithelial pyroptosis is driven by GSDMD cleavage accompanied by IL-33 processing in dry eye","volume":"18","author":"Chen","year":"2020","journal-title":"Ocul Surf"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.2147\/JIR.S310116","article-title":"Calcitriol alleviates hyperosmotic stress-induced corneal epithelial cell damage via inhibiting the NLRP3-ASC-caspase-1-GSDMD pyroptosis pathway in dry eye disease","volume":"14","author":"Zhang","year":"2021","journal-title":"J Inflamm Res"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature22393","article-title":"Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin","volume":"547","author":"Wang","year":"2017","journal-title":"Nature"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"14128","DOI":"10.1038\/ncomms14128","article-title":"Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic\/pyroptotic cell death","volume":"8","author":"Rogers","year":"2017","journal-title":"Nat Commun"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"188635","DOI":"10.1016\/j.bbcan.2021.188635","article-title":"The multifaceted roles of gasdermins in cancer biology and oncologic therapies","volume":"1876","author":"Sarrio","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1093\/jnen\/nlaa023","article-title":"Gasdermine E-dependent mitochondrial pyroptotic pathway in dermatomyositis: a possible mechanism of perifascicular atrophy","volume":"79","author":"Liu","year":"2020","journal-title":"J Neuropathol Exp Neurol"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"109265","DOI":"10.1016\/j.celrep.2021.109265","article-title":"Gasdermin-E-mediated pyroptosis participates in the pathogenesis of Crohn's disease by promoting intestinal inflammation","volume":"35","author":"Tan","year":"2021","journal-title":"Cell Rep"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s41401-020-0434-2","article-title":"Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure","volume":"42","author":"Xu","year":"2021","journal-title":"Acta Pharmacol Sin"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"117186","DOI":"10.1016\/j.lfs.2019.117186","article-title":"Bnip3 mediates doxorubicin-induced cardiomyocyte pyroptosis via caspase-3\/GSDME","volume":"242","author":"Zheng","year":"2020","journal-title":"Life Sci"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"101553","DOI":"10.1016\/j.jbc.2021.101553","article-title":"Gasdermin E mediates photoreceptor damage by all-trans-retinal in the mouse retina","volume":"298","author":"Cai","year":"2022","journal-title":"J Biol Chem"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.cmet.2020.11.018","article-title":"Apaf-1 pyroptosome senses mitochondrial permeability transition","volume":"33","author":"Xu","year":"2021","journal-title":"Cell Metab"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1167\/iovs.65.1.34","article-title":"KCNK5 regulating potassium efflux and inducing pyroptosis in corneal epithelial cells through TNFSF10-mediated autophagy in dry eye","volume":"65","author":"Liao","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","article-title":"A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V","volume":"184","author":"Vermes","year":"1995","journal-title":"J Immunol Methods"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/s41580-020-0270-8","article-title":"Emerging connectivity of programmed cell death pathways and its physiological implications","volume":"21","author":"Bedoui","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"311","DOI":"10.2147\/NDT.S172334","article-title":"Depressed mood induction in early cigarette withdrawal is unaffected by acute monoamine precursor supplementation","volume":"15","author":"Dowlati","year":"2019","journal-title":"Neuropsychiatr Dis Treat"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S1542-0124(12)70086-1","article-title":"Research in dry eye: report of the Research Subcommittee of the International Dry Eye Work Shop (2007)","volume":"5","year":"2007","journal-title":"Ocul Surf"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jtos.2021.05.006","article-title":"The physical and mental burden of dry eye disease: a large population-based study investigating the relationship with health-related quality of life and its determinants","volume":"21","author":"Morthen","year":"2021","journal-title":"Ocul Surf"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1097\/ICO.0000000000000464","article-title":"Depression, stress, quality of life, and dry eye disease in Korean women: a population-based study","volume":"34","author":"Na","year":"2015","journal-title":"Cornea"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"108294","DOI":"10.1016\/j.exer.2020.108294","article-title":"Inflammatory basis for dry eye disease flares","volume":"201","author":"Perez","year":"2020","journal-title":"Exp Eye Res"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1016\/j.ophtha.2017.07.010","article-title":"The pathophysiology of dry eye disease: what we know and future directions for research","volume":"124","author":"Pflugfelder","year":"2017","journal-title":"Ophthalmology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/ICL.0000000000000042","article-title":"The core mechanism of dry eye disease is inflammation","volume":"40","author":"Wei","year":"2014","journal-title":"Eye Contact Lens"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1038\/ni.1960","article-title":"Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria","volume":"11","author":"Miao","year":"2010","journal-title":"Nat Immunol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J Immunol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1002\/1529-0131(199908)42:8&lt;1577::AID-ANR3&gt;3.0.CO;2-Z","article-title":"Interleukin-1beta-converting enzyme\/caspase-1 in human osteoarthritic tissues: localization and role in the maturation of interleukin-1beta and interleukin-18","volume":"42","author":"Saha","year":"1999","journal-title":"Arthritis Rheum"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion","volume":"25","author":"He","year":"2015","journal-title":"Cell Res"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores","volume":"535","author":"Liu","year":"2016","journal-title":"Nature"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/s41419-023-06382-y","article-title":"The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles","volume":"14","author":"Hu","year":"2023","journal-title":"Cell Death Dis"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2147\/DMSO.S242136","article-title":"Caspase-3 promotes diabetic kidney disease through gasdermin e-mediated progression to secondary necrosis during apoptosis","volume":"13","author":"Wen","year":"2020","journal-title":"Diabetes Metab Syndr Obes"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41586-020-2071-9","article-title":"Gasdermin E suppresses tumour growth by activating anti-tumour immunity","volume":"579","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1177\/000348941212100310","article-title":"DFNA5, a gene involved in hearing loss and cancer: a review","volume":"121","author":"de Beeck","year":"2012","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/s41467-019-09397-2","article-title":"Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation","volume":"10","author":"Rogers","year":"2019","journal-title":"Nat Commun"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.trecan.2020.12.002","article-title":"GSDME: a potential ally in cancer detection and treatment","volume":"7","author":"Ibrahim","year":"2021","journal-title":"Trends Cancer"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13148-018-0479-y","article-title":"Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer","volume":"10","author":"Croes","year":"2018","journal-title":"Clin Epigenetics"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1002\/cam4.2103","article-title":"Methylation analysis of Gasdermin E shows great promise as a biomarker for colorectal cancer","volume":"8","author":"Ibrahim","year":"2019","journal-title":"Cancer Med"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/s41419-019-1883-8","article-title":"The role of pyroptosis in cancer: pro-cancer or pro-\u201chost\u201d?","volume":"10","author":"Xia","year":"2019","journal-title":"Cell Death Dis"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"3624","DOI":"10.1038\/sj.onc.1211021","article-title":"Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma","volume":"27","author":"Kim","year":"2008","journal-title":"Oncogene"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/j.1349-7006.2006.00351.x","article-title":"Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer","volume":"98","author":"Akino","year":"2007","journal-title":"Cancer Sci"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.immuni.2019.05.020","article-title":"Caspases in cell death, inflammation, and disease","volume":"50","author":"Van Opdenbosch","year":"2019","journal-title":"Immunity"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ceb.2003.10.009","article-title":"Mechanisms of caspase activation","volume":"15","author":"Boatright","year":"2003","journal-title":"Curr Opin Cell Biol"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1126\/science.1252809","article-title":"Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure","volume":"344","author":"Segawa","year":"2014","journal-title":"Science"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0165-6147(99)01292-4","article-title":"Poly (ADP-ribose) polymerase, nitric oxide and cell death","volume":"20","author":"Pieper","year":"1999","journal-title":"Trends Pharmacol Sci"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jaut.2017.02.006","article-title":"Mitochondrial DNA oxidation induces imbalanced activity of NLRP3\/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye","volume":"80","author":"Chi","year":"2017","journal-title":"J Autoimmun"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1038\/s41423-021-00740-6","article-title":"NLRP3 inflammasome activation and cell death","volume":"18","author":"Huang","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"bib53","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":"bib54","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.exer.2015.02.013","article-title":"Reactive oxygen species activated NLRP3 inflammasomes initiate inflammation in hyperosmolarity stressed human corneal epithelial cells and environment-induced dry eye patients","volume":"134","author":"Zheng","year":"2015","journal-title":"Exp Eye Res"},{"key":"bib55","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.2147\/IJN.S403337","article-title":"Suppression of NLRP3\/caspase-1\/GSDMD mediated corneal epithelium pyroptosis using melatonin-loaded liposomes to inhibit benzalkonium chloride-induced dry eye disease","volume":"18","author":"Lou","year":"2023","journal-title":"Int J Nanomedicine"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:00Z","timestamp":1791927120000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,2]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.66.1.24","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}