{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:08:51Z","timestamp":1793304531391,"version":"4.5.0"},"reference-count":43,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"14","license":[{"start":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T00:00:00Z","timestamp":1543276800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2018,11,27]]},"DOI":"10.1167\/iovs.17-23402","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T18:00:34Z","timestamp":1543341634000},"page":"DES163","source":"Crossref","is-referenced-by-count":249,"title":["Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease"],"prefix":"10.1167","volume":"59","author":[{"given":"Murat","family":"Dogru","sequence":"first","affiliation":[{"name":"Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kojima","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Simsek","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-59-14-DES163-b01","doi-asserted-by":"crossref","unstructured":"Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24: 981\u2013 990.","DOI":"10.1016\/j.cellsig.2012.01.008"},{"key":"i1552-5783-59-14-DES163-b02","doi-asserted-by":"crossref","unstructured":"Dickinson BC, Chang CJ. Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat Chem Biol. 2011; 7: 504\u2013 511.","DOI":"10.1038\/nchembio.607"},{"key":"i1552-5783-59-14-DES163-b03","doi-asserted-by":"crossref","unstructured":"Wakamatsu TH, Dogru M, Tsubota K. Tearful relations: oxidative stress, inflammation and eye diseases. Arq Bras Oftalmol. 2008; 71: 72\u2013 79.","DOI":"10.1590\/S0004-27492008000700015"},{"key":"i1552-5783-59-14-DES163-b04","doi-asserted-by":"crossref","unstructured":"Tsubota K, Kawashima M, Inaba T, et al. The antiaging approach for the treatment of dry eye. Cornea. 2012; 31 (suppl 1): S3\u2013 S8.","DOI":"10.1097\/ICO.0b013e31826a05a8"},{"key":"i1552-5783-59-14-DES163-b05","doi-asserted-by":"crossref","unstructured":"Spector A. Oxidative stress-induced cataract: mechanism of action. FASEB J. 1995; 9: 1173\u2013 1182.","DOI":"10.1096\/fasebj.9.12.7672510"},{"key":"i1552-5783-59-14-DES163-b06","doi-asserted-by":"crossref","unstructured":"Imamura Y, Noda S, Hashizume K, et al. Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration. Proc Natl Acad Sci U S A. 2006; 103: 11282\u2013 11287.","DOI":"10.1073\/pnas.0602131103"},{"key":"i1552-5783-59-14-DES163-b07","doi-asserted-by":"crossref","unstructured":"Gritz DC, Montes C, Atalla LR, Wu GS, Sevanian A, Rao NA. Histochemical localization of superoxide production in experimental autoimmune uveitis. Curr Eye Res. 1991; 10: 927\u2013 931.","DOI":"10.3109\/02713689109020328"},{"key":"i1552-5783-59-14-DES163-b08","doi-asserted-by":"crossref","unstructured":"Niesman MR, Johnson KA, Penn JS. Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochem Res. 1997; 22: 597\u2013 605.","DOI":"10.1023\/A:1022474120512"},{"key":"i1552-5783-59-14-DES163-b09","unstructured":"Alio JL, Artola A, Serra A, Ayala MJ, Mulet ME. Effect of topical antioxidant therapy on experimental infectious keratitis. Cornea. 1995; 14: 175\u2013 179."},{"key":"i1552-5783-59-14-DES163-b10","doi-asserted-by":"crossref","unstructured":"Alio JL, Ayala MJ, Mulet ME, Artola A, Ruiz JM, Bellot J. Antioxidant therapy in the treatment of experimental acute corneal inflammation. Ophthalmic Res. 1995; 27: 136\u2013 143.","DOI":"10.1159\/000267648"},{"key":"i1552-5783-59-14-DES163-b11","doi-asserted-by":"crossref","unstructured":"Ohashi Y, Dogru M, Tsubota K. Laboratory findings in tear fluid analysis. Clin Chim Acta. 2006; 369: 17\u2013 28.","DOI":"10.1016\/j.cca.2005.12.035"},{"key":"i1552-5783-59-14-DES163-b12","doi-asserted-by":"crossref","unstructured":"Avalos I, Chung CP, Oeser A, et al. Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms. Lupus. 2007; 16: 195\u2013 200.","DOI":"10.1177\/0961203306075802"},{"key":"i1552-5783-59-14-DES163-b13","doi-asserted-by":"crossref","unstructured":"Bohanec Grabar P, Logar D, Tom\u0161ic M, Rozman B, Dol\u017ean V . Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients. Dis Markers. 2009; 26: 41\u2013 48.","DOI":"10.1155\/2009\/147356"},{"key":"i1552-5783-59-14-DES163-b14","doi-asserted-by":"crossref","unstructured":"Giusti L, Baldini C, Bazzichi L, et al. Proteome analysis of whole saliva: a new tool for rheumatic diseases--the example of Sjogren's syndrome. Proteomics. 2007; 7: 1634\u2013 1643.","DOI":"10.1002\/pmic.200600783"},{"key":"i1552-5783-59-14-DES163-b15","doi-asserted-by":"crossref","unstructured":"Mukhopadhyay S, Sen S, Majhi B, Das K, Kar M. Methyl glyoxal elevation is associated with oxidative stress in rheumatoid arthritis. Free Radic Res. 2007; 41: 507\u2013 514.","DOI":"10.1080\/10715760601148285"},{"key":"i1552-5783-59-14-DES163-b16","doi-asserted-by":"crossref","unstructured":"Miyata T, Ishiguro N, Yasuda Y, et al. Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers. Biochem Biophys Res Commun. 1998; 244: 45\u2013 49.","DOI":"10.1006\/bbrc.1998.8203"},{"key":"i1552-5783-59-14-DES163-b17","doi-asserted-by":"crossref","unstructured":"Lemarechal H, Anract P, Beaudeux JL, Bonnefont-Rousselot D, Ekindjian OG, Borderie D. Impairment of thioredoxin reductase activity by oxidative stress in human rheumatoid synoviocytes. Free Radic Res. 2007; 41: 688\u2013 698.","DOI":"10.1080\/10715760701294468"},{"key":"i1552-5783-59-14-DES163-b18","unstructured":"Kurimoto C, Kawano S, Tsuji G, et al. Thioredoxin may exert a protective effect against tissue damage caused by oxidative stress in salivary glands of patients with Sj\u00f6gren's syndrome. J Rheumatol. 2007; 34: 2035\u2013 2043."},{"key":"i1552-5783-59-14-DES163-b19","doi-asserted-by":"crossref","unstructured":"Bashir S, Harris G, Denman MA, Blake DR, Winyard PG. Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann Rheum Dis. 1993; 52: 659\u2013 666.","DOI":"10.1136\/ard.52.9.659"},{"key":"i1552-5783-59-14-DES163-b20","unstructured":"Cejkova J, Ardan T, Jirsova K, et al. The role of conjunctival epithelial cell xanthine oxidoreductase\/xanthine oxidase in oxidative reactions on the ocuiar surface of dry eye patients with Sjogren's syndrome. Histol Histopathol. 2007; 22: 997."},{"key":"i1552-5783-59-14-DES163-b21","unstructured":"Cejkova J, Ardan T, Simonova Z, et al. Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sj\u00f6gren's syndrome) and its possible contribution to the development of ocular surface oxidative injuries. Histol Histopathol. 2008; 23: 1477\u2013 1483."},{"key":"i1552-5783-59-14-DES163-b22","doi-asserted-by":"crossref","unstructured":"Choi W, Lian C, Ying L, et al. Expression of lipid peroxidation markers in the tear film and ocular surface of patients with non-Sjogren syndrome: potential biomarkers for dry eye disease. Curr Eye Res. 2016; 41: 1143\u2013 1149.","DOI":"10.3109\/02713683.2015.1098707"},{"key":"i1552-5783-59-14-DES163-b23","doi-asserted-by":"crossref","unstructured":"Wakamatsu TH, Dogru M, Matsumoto Y, et al. Evaluation of lipid oxidative stress status in Sjogren syndrome patients. Invest Ophthalmol Vis Sci. 2013; 54: 201\u2013 210.","DOI":"10.1167\/iovs.12-10325"},{"key":"i1552-5783-59-14-DES163-b24","unstructured":"Cavet ME, Harrington KL, Vollmer TR, Ward KW, Zhang J-Z. Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells. Mol Vis. 2011; 17: 533."},{"key":"i1552-5783-59-14-DES163-b25","doi-asserted-by":"crossref","unstructured":"Macri A, Scanarotti C, Bassi AM, et al. Evaluation of oxidative stress levels in the conjunctival epithelium of patients with or without dry eye, and dry eye patients treated with preservative-free hyaluronic acid 0.15% and vitamin B12 eye drops. Graefe's Arch Clin Exp Ophthalmol. 2015; 253: 425\u2013 430.","DOI":"10.1007\/s00417-014-2853-6"},{"key":"i1552-5783-59-14-DES163-b26","doi-asserted-by":"crossref","unstructured":"Li Y, Liu H, Zeng W, Wei J. Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells. PLoS One. 2017; 12: e0174437.","DOI":"10.1371\/journal.pone.0174437"},{"key":"i1552-5783-59-14-DES163-b27","doi-asserted-by":"crossref","unstructured":"Chen H-C, Chen Z-Y, Wang T-J, et al. Herbal supplement in a buffer for dry eye syndrome treatment. Int J Mol Sci. 2017; 18: 1697.","DOI":"10.3390\/ijms18081697"},{"key":"i1552-5783-59-14-DES163-b28","unstructured":"Batista TM, Tomiyoshi LM, Dias AC, et al. Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles. Mol Vis. 2012; 18: 194\u2013 202."},{"key":"i1552-5783-59-14-DES163-b29","doi-asserted-by":"crossref","unstructured":"Bucolo C, Fidilio A, Platania CBM, Geraci F, Lazzara F, Drago F. Antioxidant and osmoprotecting activity of taurine in dry eye models. J Ocul Pharmacol Ther. 2018; 34: 188\u2013 194.","DOI":"10.1089\/jop.2017.0008"},{"key":"i1552-5783-59-14-DES163-b30","doi-asserted-by":"crossref","unstructured":"Nezzar H, Mbekeani JN, Noblanc A, Chiambaretta F, Drevet JR, Kocer A. Investigation of antioxidant systems in human meibomian gland and conjunctival tissues. Exp Eye Res. 2017; 165: 99\u2013 104.","DOI":"10.1016\/j.exer.2017.09.005"},{"key":"i1552-5783-59-14-DES163-b31","doi-asserted-by":"crossref","unstructured":"Nakamura S, Shibuya M, Nakashima H, et al. Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye. Invest Ophthalmol Vis Sci. 2007; 48: 1552\u2013 1558.","DOI":"10.1167\/iovs.06-1027"},{"key":"i1552-5783-59-14-DES163-b32","doi-asserted-by":"crossref","unstructured":"Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993; 4: 197\u2013 250.","DOI":"10.1177\/10454411930040020401"},{"key":"i1552-5783-59-14-DES163-b33","unstructured":"Behndig A, Karlsson K, Johansson BO, Brannstrom T, Marklund SL. Superoxide dismutase isoenzymes in the normal and diseased human cornea. Invest Ophthalmol Vis Sci. 2001; 42: 2293\u2013 2296."},{"key":"i1552-5783-59-14-DES163-b34","doi-asserted-by":"crossref","unstructured":"Kojima T, Wakamatsu TH, Dogru M, et al. Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. Am J Pathol. 2012; 180: 1879\u2013 1896.","DOI":"10.1016\/j.ajpath.2012.01.019"},{"key":"i1552-5783-59-14-DES163-b35","doi-asserted-by":"crossref","unstructured":"Kojima T, Dogru M, Ibrahim OM, et al. Effects of oxidative stress on the conjunctiva in Cu, Zn-superoxide dismutase-1 (Sod1)-Knockout Mice. Invest Ophthalmol Vis Sci. 2015; 56: 8382\u2013 8391.","DOI":"10.1167\/iovs.15-18295"},{"key":"i1552-5783-59-14-DES163-b36","doi-asserted-by":"crossref","unstructured":"Ibrahim OM, Dogru M, Matsumoto Y, et al. Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. PLoS One. 2014; 9: e99328.","DOI":"10.1371\/journal.pone.0099328"},{"key":"i1552-5783-59-14-DES163-b37","doi-asserted-by":"crossref","unstructured":"Motohashi H, Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med. 2004; 10: 549\u2013 557.","DOI":"10.1016\/j.molmed.2004.09.003"},{"key":"i1552-5783-59-14-DES163-b38","doi-asserted-by":"crossref","unstructured":"Cano M, Thimmalappula R, Fujihara M, et al. Cigarette smoking, oxidative stress, the anti-oxidant response through Nrf2 signaling, and age-related macular degeneration. Vis Res. 2010; 50: 652\u2013 664.","DOI":"10.1016\/j.visres.2009.08.018"},{"key":"i1552-5783-59-14-DES163-b39","doi-asserted-by":"crossref","unstructured":"Kojima T, Dogru M, Higuchi A, et al. The effect of Nrf2 knockout on ocular surface protection from acute tobacco smoke exposure: evidence from Nrf2 knockout mice. Am J Pathol. 2015; 185: 776\u2013 785.","DOI":"10.1016\/j.ajpath.2014.11.014"},{"key":"i1552-5783-59-14-DES163-b40","doi-asserted-by":"crossref","unstructured":"Uchino Y, Kawakita T, Ishii T, Ishii N, Tsubota K. A new mouse model of dry eye disease: oxidative stress affects functional decline in the lacrimal gland. Cornea. 2012; 31 (suppl 1): S63\u2013 S67.","DOI":"10.1097\/ICO.0b013e31826a5de1"},{"key":"i1552-5783-59-14-DES163-b41","doi-asserted-by":"crossref","unstructured":"Kawashima M, Kawakita T, Okada N, et al. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats. Biochem Biophys Res Commun. 2010; 397: 724\u2013 728.","DOI":"10.1016\/j.bbrc.2010.06.018"},{"key":"i1552-5783-59-14-DES163-b42","doi-asserted-by":"crossref","unstructured":"Kawashima M, Kawakita T, Inaba T, et al. Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice. PLoS One. 2012; 7: e33148.","DOI":"10.1371\/journal.pone.0033148"},{"key":"i1552-5783-59-14-DES163-b43","doi-asserted-by":"crossref","unstructured":"Higuchi A, Inoue H, Kaneko Y, Oonishi E, Tsubota K. Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals. Sci Rep. 2016; 6: 36903.","DOI":"10.1038\/srep36903"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2717228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:30:51Z","timestamp":1791927051000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.17-23402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,27]]},"references-count":43,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2018,11,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.17-23402","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2018,11,27]]}}}