{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:14:19Z","timestamp":1792196059458,"version":"4.4.0"},"reference-count":61,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"4","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"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":[[2024,4,22]]},"DOI":"10.1167\/iovs.65.4.33","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T12:30:50Z","timestamp":1716294650000},"page":"33","source":"Crossref","is-referenced-by-count":30,"title":["Mitochondrial DNA-Activated cGAS-STING Signaling in Environmental Dry Eye"],"prefix":"10.1167","volume":"65","author":[{"given":"Xiying","family":"Tan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifen","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"7","key":"bib1","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1111\/aos.v100.7","article-title":"Video display terminal use and dry eye: preventive measures and future perspectives","volume":"100","author":"Kam\u00f8y","year":"2022","journal-title":"Acta Ophthalmol"},{"issue":"11S","key":"bib2","doi-asserted-by":"crossref","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 Nov","journal-title":"Ophthalmology"},{"issue":"1","key":"bib3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12886-018-0700-y","article-title":"Short-term effect of a developed warming moist chamber goggle for video display terminal-associated dry eye","volume":"18","author":"Ren","year":"2018","journal-title":"BMC Ophthalmol"},{"issue":"5","key":"bib4","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.ophtha.2010.08.033","article-title":"Tear dynamics and corneal confocal microscopy of subjects with mild self-reported office dry eye","volume":"118","author":"Zhang","year":"2011","journal-title":"Ophthalmology"},{"key":"bib5","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"},{"issue":"17","key":"bib6","doi-asserted-by":"publisher","first-page":"e2200435","DOI":"10.1002\/advs.v9.17","article-title":"Anti-oxidative and anti-inflammatory micelles: break the dry eye vicious cycle","volume":"9","author":"Li","year":"2022","journal-title":"Adv Sci (Weinh)"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.exer.2005.08.019","article-title":"JNK and ERK MAP kinases mediate induction of IL-1\u00df, TNF-a and IL-8 following hyperosmolar stress in human limbal epithelial cells","volume":"82","author":"Li","year":"2006","journal-title":"Exp. Eye Res."},{"issue":"12","key":"bib8","doi-asserted-by":"publisher","first-page":"4293","DOI":"10.1167\/iovs.03-1145","article-title":"Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface","volume":"45","author":"Luo","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"14","key":"bib9","doi-asserted-by":"publisher","first-page":"DES163","DOI":"10.1167\/iovs.17-23402","article-title":"Potential role of oxidative stress in ocular surface inflammation and dry eye disease","volume":"59","author":"Dogru","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"bib10","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1111\/aos.2018.96.issue-4","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol"},{"issue":"8","key":"bib11","doi-asserted-by":"publisher","first-page":"102867","DOI":"10.1016\/j.autrev.2021.102867","article-title":"Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: potential role in Sj\u00f6gren's syndrome","volume":"20","author":"Barrera","year":"2021","journal-title":"Autoimmun Rev"},{"key":"bib12","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"},{"issue":"3","key":"bib13","doi-asserted-by":"publisher","first-page":"537","DOI":"10.3390\/cells10030537","article-title":"Cell death and inflammation: the role of mitochondria in health and disease","volume":"10","author":"Picca","year":"2021","journal-title":"Cells"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"195","DOI":"10.15698\/cst","article-title":"The sensing of mitochondrial DAMPs by non-immune cells","volume":"3","author":"Rodr\u00edguez-Nuevo","year":"2019","journal-title":"Cell Stress"},{"issue":"8","key":"bib15","doi-asserted-by":"publisher","first-page":"102867","DOI":"10.1016\/j.autrev.2021.102867","article-title":"Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: potential role in Sj\u00f6gren's syndrome","volume":"20","author":"Barrera","year":"2021","journal-title":"Autoimmun Rev"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.autrev.2011.04.011","article-title":"New autoantigens in the antiphospholipid syndrome","volume":"10","author":"Alessandri","year":"2011","journal-title":"Autoimmun Rev"},{"issue":"1","key":"bib17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3390\/genes11010086","article-title":"Mitochondrial DNA: a key regulator of anti-microbial innate immunity","volume":"11","author":"Kausar","year":"2020","journal-title":"Genes (Basel)"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","article-title":"DNA sensing by the cGAS-STING pathway in health and disease","volume":"20","author":"Motwani","year":"2019","journal-title":"Nat Rev Genet"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/nature23890","article-title":"cGAS senses long and HMGB\/TFAM- bound U-turn DNA by forming protein-DNA ladders","volume":"549","author":"Andreeva","year":"2017","journal-title":"Nature"},{"issue":"6","key":"bib20","doi-asserted-by":"publisher","first-page":"109977","DOI":"10.1016\/j.celrep.2021.109977","article-title":"TNF leads to mtDNA release and cGAS\/STING-dependent interferon responses that support inflammatory arthritis","volume":"37","author":"Willemsen","year":"2021","journal-title":"Cell Rep"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"102305","DOI":"10.1016\/j.redox.2022.102305","article-title":"XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA-cGAS-STING signaling in macrophages during acute liver injury","volume":"52","author":"Liu","year":"2022","journal-title":"Redox Biol"},{"issue":"3","key":"bib22","doi-asserted-by":"publisher","first-page":"e139333","DOI":"10.1172\/JCI139333","article-title":"ATM inhibition enhances cancer immunotherapy by promoting mtDNA leakage and cGAS\/STING activation","volume":"131","author":"Hu","year":"2021","journal-title":"J Clin Invest"},{"issue":"3","key":"bib23","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","article-title":"TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS\/STING in ALS","volume":"183","author":"Yu","year":"2020","journal-title":"Cell"},{"issue":"1","key":"bib24","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.immuni.2020.05.013","article-title":"Structures and mechanisms in the cGAS-STING innate immunity pathway","volume":"53","author":"Zhang","year":"2020","journal-title":"Immunity"},{"issue":"9","key":"bib25","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS-STING pathway as a therapeutic target in inflammatory diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"bib26","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS-STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"7454","key":"bib27","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature12305","article-title":"Structural mechanism of cytosolic DNA sensing by cGAS","volume":"498","author":"Civril","year":"2013","journal-title":"Nature"},{"issue":"7","key":"bib28","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nsmb.2332","article-title":"Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP","volume":"19","author":"Shang","year":"2012","journal-title":"Nat Struct Mol Biol"},{"issue":"7","key":"bib29","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nsmb.2331","article-title":"Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system","volume":"19","author":"Shu","year":"2012","journal-title":"Nat Struct Mol Biol"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.cell.2013.07.023","article-title":"Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA","volume":"154","author":"Gao","year":"2013","journal-title":"Cell"},{"issue":"2","key":"bib31","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.cell.2019.05.036","article-title":"STING polymer structure reveals mechanisms for activation, hyperactivation, and inhibition","volume":"178","author":"Ergun","year":"2019","journal-title":"Cell"},{"issue":"7748","key":"bib32","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41586-019-0998-5","article-title":"Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP","volume":"567","author":"Shang","year":"2019","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"11932","DOI":"10.1038\/ncomms11932","article-title":"Activation of STING requires palmitoylation at the Golgi","volume":"7","author":"Mukai","year":"2016","journal-title":"Nat. Commun."},{"issue":"9","key":"bib34","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1038\/s41418-022-00967-4","article-title":"Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced retina inflammation and degeneration","volume":"29","author":"Zou","year":"2022","journal-title":"Cell Death Differ"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"108366","DOI":"10.1016\/j.exer.2020.108366","article-title":"The cGAS-STING signaling pathway contributes to the inflammatory response and autophagy in Aspergillus fumigatus keratitis","volume":"202","author":"Han","year":"2021","journal-title":"Exp Eye Res"},{"issue":"21","key":"bib36","doi-asserted-by":"publisher","first-page":"11080","DOI":"10.1128\/JVI.00954-15","article-title":"Role of the DNA sensor STING in protection from lethal infection following corneal and intracerebral challenge with herpes simplex virus 1","volume":"89","author":"Parker","year":"2015","journal-title":"J Virol"},{"issue":"4","key":"bib37","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/mi.2015.124","article-title":"A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin","volume":"9","author":"Royer","year":"2016","journal-title":"Mucosal Immunol"},{"issue":"1","key":"bib38","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41392-023-01624-z","article-title":"The cGAS-STING pathway-dependent sensing of mitochondrial DNA mediates ocular surface inflammation","volume":"8","author":"Ouyang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"4","key":"bib39","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1167\/iovs.07-0744","article-title":"A murine model of dry eye induced by an intelligently controlled environmental system","volume":"49","author":"Chen","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"bib40","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1097\/ICL.0000000000000742","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"},{"issue":"1","key":"bib41","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12964-020-00637-3","article-title":"Mitochondrial DNA drives noncanonical inflammation activation via cGAS-STING signaling pathway in retinal microvascular endothelial cells","volume":"18","author":"Guo","year":"2020","journal-title":"Cell Commun Signal"},{"issue":"1","key":"bib42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40659-022-00390-6","article-title":"Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats","volume":"55","author":"Guo","year":"2022","journal-title":"Biol Res"},{"issue":"4","key":"bib43","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1002\/art.v69.4","article-title":"Expression of cyclic GMP-AMP synthase in patients with systemic lupus erythematosus","volume":"69","author":"An","year":"2017","journal-title":"Arthritis Rheumatol"},{"issue":"10","key":"bib44","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1136\/annrheumdis-2018-212988","article-title":"Apoptosis-derived membrane vesicles drive the cGAS-STING pathway and enhance type I IFN production in systemic lupus erythematosus","volume":"77","author":"Kato","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"101530","DOI":"10.1016\/j.isci.2020.101530","article-title":"STING mediates lupus via the activation of conventional dendritic cell maturation and plasmacytoid dendritic cell differentiation","volume":"23","author":"Thim-uam","year":"2020","journal-title":"iScience"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"105791","DOI":"10.1016\/j.intimp.2019.105791","article-title":"Accumulation of cytosolic dsDNA contributes to fibroblast-like synoviocytes-mediated rheumatoid arthritis synovial inflammation","volume":"76","author":"Wang","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"bib47","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":"bib48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exer.2014.05.001","article-title":"Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye","volume":"125","author":"Zheng","year":"2014","journal-title":"Exp Eye Res"},{"issue":"12","key":"bib49","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1167\/iovs.63.12.18","article-title":"AMPK\/MFF activation: role in mitochondrial fission and mitophagy in dry eye [published correction appears in Invest Ophthalmol Vis Sci. 2022;63(13):24]","volume":"63","author":"Peng","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"8","key":"bib50","doi-asserted-by":"publisher","first-page":"e21757","DOI":"10.1096\/fsb2.v35.8","article-title":"Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis","volume":"35","author":"Torre-Minguela","year":"2021","journal-title":"FASEB J"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.lungcan.2009.03.027","article-title":"Phase II study of ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid\/DMXAA) 1800mg\/m (2) combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer","volume":"65","author":"McKeage","year":"2009","journal-title":"Lung Cancer"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1007\/s00262-015-1713-5","article-title":"STING activator c-di-GMP enhances the anti-tumor effects of peptide vaccines in melanoma-bearing mice","volume":"64","author":"Wang","year":"2015","journal-title":"Cancer Immunol Immunother"},{"issue":"1","key":"bib57","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/iej.v55.1","article-title":"The induction of inflammation by the cGAS-STING pathway in human dental pulp cells: a laboratory investigation","volume":"55","author":"Tian","year":"2022","journal-title":"Int Endod J"},{"issue":"8","key":"bib58","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1038\/s41401-021-00813-2","article-title":"STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion","volume":"43","author":"Wu","year":"2022","journal-title":"Acta Pharmacol Sin"},{"issue":"7747","key":"bib59","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41586-019-1006-9","article-title":"Autophagy induction via STING trafficking is a primordial function of the cGAS pathway","volume":"567","author":"Gui","year":"2019","journal-title":"Nature"},{"issue":"1","key":"bib60","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13046-022-02262-z","article-title":"Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway","volume":"41","author":"Li","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"issue":"1","key":"bib61","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13075-022-02860-4","article-title":"The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sj\u00f6gren's syndrome","volume":"24","author":"Peng","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"bib53","author":"Chinook Therapeutics, Inc. (formerly Aduro)"},{"key":"bib54","author":"Merck Sharp & Dohme LLC"},{"key":"bib55","author":"GlaxoSmithKline"},{"key":"bib56","author":"Eisai Inc","year":"2023"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2793598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:52Z","timestamp":1791927112000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2793598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.4.33","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,4,22]]}}}