{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:21:25Z","timestamp":1792894885116,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>Dry eye disease (DED) is a chronic ocular surface disorder, associated with inflammation, which can cause severe morbidity, visual compromise, and loss of quality of life, affecting up to 5\u201350% of the world population. In DED, ocular surface damage and tear film instability due to abnormal tear secretion lead to ocular surface pain, discomfort, and epithelial barrier disruption. Studies have shown the involvement of autophagy regulation in dry eye disease as a pathogenic mechanism along with the inflammatory response. Autophagy is a self-degradation pathway in mammalian cells that reduces the excessive inflammation driven by the secretion of inflammatory factors in tears. Specific autophagy modulators are already available for the management of DED currently. However, growing studies on autophagy regulation in DED might further encourage the development of autophagy modulating drugs that reduce the pathological response at the ocular surface. In this review, we summarize the role of autophagy in the pathogenesis of dry eye disease and explore its therapeutic application.<\/jats:p>","DOI":"10.4103\/ijo.ijo_2912_22","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T11:10:52Z","timestamp":1680952252000},"page":"1285-1291","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface"],"prefix":"10.4103","volume":"71","author":[{"given":"Nallathambi","family":"Jeyabalan","sequence":"first","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Narayana Nethralaya Eye Hospital, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswathi M","family":"Pillai","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Narayana Nethralaya Eye Hospital, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Khamar","sequence":"additional","affiliation":[{"name":"Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv R","family":"Mohan","sequence":"additional","affiliation":[{"name":"Harry S. Truman Memorial Veterans\u2019 Hospital, Columbia, MO, USA"},{"name":"Departments of Veterinary Medicine and Surgery and Biomedical Sciences, University of Missouri, Columbia, MO, USA"},{"name":"Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkasubhra","family":"Ghosh","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Narayana Nethralaya Eye Hospital, Bengaluru, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"R1-20240828","doi-asserted-by":"crossref","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":"R2-20240828","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":"R3-20240828","first-page":"71","article-title":"The pathophysiology, diagnosis, and treatment of dry eye disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Dtsch Arztebl Int"},{"key":"R4-20240828","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.clae.2013.07.008","article-title":"Rose bengal staining as an assessment of ocular surface damage and recovery in dry eye disease-a review","volume":"36","author":"Doughty","year":"2013","journal-title":"Cont Lens Anterior Eye"},{"key":"R5-20240828","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":"R6-20240828","first-page":"2609","article-title":"Conjunctival T-cell subpopulations in Sjogren's and non-Sjogren's patients with dry eye","volume":"43","author":"Stern","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R7-20240828","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jtos.2013.07.003","article-title":"Role of hyperosmolarity in the pathogenesis and management of dry eye disease:Proceedings of the OCEAN group meeting","volume":"11","author":"Baudouin","year":"2013","journal-title":"Ocul Surf"},{"key":"R8-20240828","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.exer.2007.01.015","article-title":"A single injection of interleukin-1 induces reversible aqueous-tear deficiency, lacrimal gland inflammation, and acinar and ductal cell proliferation","volume":"84","author":"Zoukhri","year":"2007","journal-title":"Exp Eye Res"},{"key":"R9-20240828","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/ncb2090","article-title":"Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition","volume":"12","author":"Luciani","year":"2010","journal-title":"Nat Cell Biol"},{"key":"R10-20240828","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nri.2016.100","article-title":"Crosstalk between autophagy and inflammatory signalling pathways:Balancing defence and homeostasis","volume":"16","author":"Cadwell","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"R11-20240828","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.1111\/aos.13526","article-title":"Dry eye disease and oxidative stress","volume":"96","author":"Seen","year":"2018","journal-title":"Acta Ophthalmol"},{"key":"R12-20240828","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.exer.2005.10.018","article-title":"Effect of inflammation on lacrimal gland function","volume":"82","author":"Zoukhri","year":"2006","journal-title":"Exp Eye Res"},{"key":"R13-20240828","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.preteyeres.2016.08.001","article-title":"Autophagy in the eye:Development, degeneration, and aging","volume":"55","author":"Boya","year":"2016","journal-title":"Prog Retin Eye Res"},{"key":"R14-20240828","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res"},{"key":"R15-20240828","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1007\/s00018-015-2034-8","article-title":"Autophagy signal transduction by ATG proteins:From hierarchies to networks","volume":"72","author":"Wesselborg","year":"2015","journal-title":"Cell Mol Life Sci"},{"key":"R16-20240828","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"R17-20240828","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40169-017-0154-5","article-title":"Autophagy and inflammation","volume":"6","author":"Qian","year":"2017","journal-title":"Clin Transl Med"},{"key":"R18-20240828","doi-asserted-by":"crossref","first-page":"e18666","DOI":"10.1371\/journal.pone.0018666","article-title":"Inflammasome-independent modulation of cytokine response by autophagy in human cells","volume":"6","author":"Crisan","year":"2011","journal-title":"PLoS One"},{"key":"R19-20240828","doi-asserted-by":"crossref","first-page":"884","DOI":"10.7150\/ijbs.15194","article-title":"Interactions between autophagy and inhibitory cytokines","volume":"12","author":"Wu","year":"2016","journal-title":"Int J Biol Sci"},{"key":"R20-20240828","doi-asserted-by":"crossref","first-page":"C73","DOI":"10.1152\/ajpcell.00110.2016","article-title":"Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis","volume":"314","author":"Vij","year":"2018","journal-title":"Am J Physiol Cell Physiol"},{"key":"R21-20240828","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.4161\/auto.20520","article-title":"LC3 as a potential therapeutic target in hypoxia-induced pulmonary hypertension","volume":"8","author":"Lahm","year":"2012","journal-title":"Autophagy"},{"key":"R22-20240828","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/MIB.0000000000000994","article-title":"The Crohn's and colitis foundation of america survey of inflammatory bowel disease patient health care access","volume":"23","author":"Rubin","year":"2017","journal-title":"Inflamm Bowel Dis"},{"key":"R23-20240828","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1167\/iovs.18-24057","article-title":"Oxidative stress suppresses cellular autophagy in corneal epithelium","volume":"59","author":"Yin","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R24-20240828","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1089\/ars.2013.5371","article-title":"An overview of autophagy:Morphology, mechanism, and regulation","volume":"20","author":"Parzych","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"R25-20240828","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1159\/000351979","article-title":"The mechanism and physiological function of macroautophagy","volume":"5","author":"Klionsky","year":"2013","journal-title":"J Innate Immun"},{"key":"R26-20240828","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s00018-011-0865-5","article-title":"Microautophagy:Lesser-known self-eating","volume":"69","author":"Li","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"R27-20240828","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","article-title":"The coming of age of chaperone-mediated autophagy","volume":"19","author":"Kaushik","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R28-20240828","doi-asserted-by":"crossref","first-page":"jcs246322","DOI":"10.1242\/jcs.246322","article-title":"Microautophagy-distinct molecular mechanisms handle cargoes of many sizes","volume":"133","author":"Schuck","year":"2020","journal-title":"J Cell Sci"},{"key":"R29-20240828","doi-asserted-by":"crossref","first-page":"17280","DOI":"10.1038\/s41598-017-17128-0","article-title":"Elevation of autophagy markers in Sjogren syndrome dry eye","volume":"7","author":"Byun","year":"2017","journal-title":"Sci Rep"},{"key":"R30-20240828","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":"R31-20240828","doi-asserted-by":"crossref","first-page":"8966","DOI":"10.3390\/ijms21238966","article-title":"Autophagy activation protects ocular surface from inflammation in a dry eye model in vitro","volume":"21","author":"Liu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"R32-20240828","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.exer.2019.04.023","article-title":"Corneal autophagy and ocular surface inflammation:A new perspective in dry eye","volume":"184","author":"Ma","year":"2019","journal-title":"Exp Eye Res"},{"key":"R33-20240828","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"R34-20240828","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2015.09.001","article-title":"Introduction to autophagy in the eye (or \u201cwhat's eatin'you?\u201d)","volume":"144","author":"Ferguson","year":"2016","journal-title":"Exp Eye Res"},{"key":"R35-20240828","doi-asserted-by":"crossref","first-page":"7627329","DOI":"10.1155\/2018\/7627329","article-title":"Chloroquine protects human corneal epithelial cells from desiccation stress induced inflammation without altering the autophagy flux","volume":"2018","author":"Shivakumar","year":"2018","journal-title":"Biomed Res Int"},{"key":"R36-20240828","doi-asserted-by":"crossref","first-page":"18146","DOI":"10.1074\/jbc.M112.436584","article-title":"Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism","volume":"288","author":"Wang","year":"2013","journal-title":"J Biol Chem"},{"key":"R37-20240828","doi-asserted-by":"crossref","first-page":"949206","DOI":"10.3389\/fimmu.2022.949206","article-title":"Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjogren's syndrome","volume":"13","author":"Cheng","year":"2022","journal-title":"Front Immunol"},{"key":"R38-20240828","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/jop.2021.0121","article-title":"Autophagy protects ocular surface against overactivated inflammation by degrading retinoic acid-induced Gene-I in human conjunctival epithelial cells","volume":"38","author":"Zhou","year":"2022","journal-title":"J Ocul Pharmacol Ther"},{"key":"R39-20240828","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jtos.2019.08.004","article-title":"Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells","volume":"17","author":"Panigrahi","year":"2019","journal-title":"Ocul Surf"},{"key":"R40-20240828","doi-asserted-by":"crossref","first-page":"108210","DOI":"10.1016\/j.exer.2020.108210","article-title":"Calcitriol inhibits apoptosis via activation of autophagy in hyperosmotic stress stimulated corneal epithelial cells in vivo and in vitro","volume":"200","author":"Lyu","year":"2020","journal-title":"Exp Eye Res"},{"key":"R41-20240828","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1167\/iovs.19-27072","article-title":"Induction of DDIT4 impairs autophagy through oxidative stress in dry eye","volume":"60","author":"Wang","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R42-20240828","doi-asserted-by":"crossref","first-page":"108491","DOI":"10.1016\/j.exer.2021.108491","article-title":"Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye","volume":"205","author":"Wang","year":"2021","journal-title":"Exp Eye Res"},{"key":"R43-20240828","doi-asserted-by":"crossref","first-page":"799949","DOI":"10.3389\/fmed.2021.799949","article-title":"WAY-100635 alleviates corneal lesions through 5-HT1A receptor-ROS-autophagy axis in dry eye","volume":"8","author":"Zhou","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"R44-20240828","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1167\/iovs.61.10.26","article-title":"Trehalose induces autophagy against inflammation by activating TFEB signaling pathway in human corneal epithelial cells exposed to hyperosmotic stress","volume":"61","author":"Liu","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R45-20240828","doi-asserted-by":"crossref","first-page":"292139","DOI":"10.1155\/2014\/292139","article-title":"Trehalose-based eye drops preserve viability and functionality of cultured human corneal epithelial cells during desiccation","volume":"2014","author":"Hill-Bator","year":"2014","journal-title":"Biomed Res Int"},{"key":"R46-20240828","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1089\/jop.2020.0119","article-title":"Commercially available eye drops containing trehalose protect against dry conditions via autophagy induction","volume":"37","author":"Hernandez","year":"2021","journal-title":"J Ocul Pharmacol Ther"},{"key":"R47-20240828","doi-asserted-by":"crossref","first-page":"100070","DOI":"10.1074\/jbc.RA120.015833","article-title":"Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis","volume":"296","author":"Georgiev","year":"2021","journal-title":"J Biol Chem"},{"key":"R48-20240828","doi-asserted-by":"crossref","first-page":"e1309","DOI":"10.1038\/cddis.2014.260","article-title":"Activation of HIF-1alpha (hypoxia inducible factor-1alpha) prevents dry eye-induced acinar cell death in the lacrimal gland","volume":"5","author":"Seo","year":"2014","journal-title":"Cell Death Dis"},{"key":"R49-20240828","doi-asserted-by":"crossref","first-page":"3708","DOI":"10.1167\/iovs.19-27469","article-title":"The effect of chloroquine on the development of dry eye in Sjogren syndrome animal model","volume":"60","author":"Lee","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R50-20240828","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1167\/iovs.16-19159","article-title":"Rapamycin eye drops suppress lacrimal gland inflammation in a murine model of Sjogren's syndrome","volume":"58","author":"Shah","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R51-20240828","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":"Martinez-Chacon","year":"2020","journal-title":"Mol Cell Biochem"},{"key":"R52-20240828","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1080\/14656566.2017.1372748","article-title":"Lifitegrast for the treatment of dry eye disease in adults","volume":"18","author":"Donnenfeld","year":"2017","journal-title":"Expert Opin Pharmacother"},{"key":"R53-20240828","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.fct.2018.06.054","article-title":"Mechanism of cyclosporine A nephrotoxicity:Oxidative stress, autophagy, and signalings","volume":"118","author":"Wu","year":"2018","journal-title":"Food Chem Toxicol"}],"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2912_22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:13:24Z","timestamp":1787166804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2912_22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_2912_22","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"2022-11-02","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}