{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:37Z","timestamp":1787028457873,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT)","award":["2019M3A9I309169911"],"award-info":[{"award-number":["2019M3A9I309169911"]}]},{"name":"General Research Program of the National Research Foundation (NRF) funded by the Korean government (MSIT)","award":["2020R1F1A1072506"],"award-info":[{"award-number":["2020R1F1A1072506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fucosylation is involved in a wide range of biological processes from cellular adhesion to immune regulation. Although the upregulation of fucosylated glycans was reported in diseased corneas, its implication in ocular surface disorders remains largely unknown. In this study, we analyzed the expression of a fucosylated glycan on the ocular surface in two mouse models of dry eye disease (DED), the NOD.B10.H2b mouse model and the environmental desiccating stress model. We furthermore investigated the effects of aberrant fucosylation inhibition on the ocular surface and DED. Results demonstrated that the level of type 2 H antigen, an \u03b1(1,2)-fucosylated glycan, was highly increased in the cornea and conjunctiva both in NOD.B10.H2b mice and in BALB\/c mice subjected to desiccating stress. Inhibition of \u03b1(1,2)-fucosylation by 2-deoxy-D-galactose (2-D-gal) reduced corneal epithelial defects and increased tear production in both DED models. Moreover, 2-D-gal treatment suppressed the levels of inflammatory cytokines in the ocular surface and the percentages of IFN-\u03b3+CD4+ cells in draining lymph nodes, whereas it did not affect the number of conjunctival goblet cells, the MUC5AC level or the meibomian gland area. Together, the findings indicate that aberrant fucosylation underlies the pathogenesis of DED and may be a novel target for DED therapy.<\/jats:p>","DOI":"10.3390\/ijms22157863","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T10:31:44Z","timestamp":1627036304000},"page":"7863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of Aberrant \u03b1(1,2)-Fucosylation at Ocular Surface Ameliorates Dry Eye Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2203-5709","authenticated-orcid":false,"given":"Chang Ho","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea"},{"name":"Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Suk","family":"Ryu","sequence":"additional","affiliation":[{"name":"Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hwa","family":"Ko","sequence":"additional","affiliation":[{"name":"Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7899-5314","authenticated-orcid":false,"given":"Joo Youn","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea"},{"name":"Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.chembiol.2018.02.005","article-title":"Unmasking Fucosylation: From Cell Adhesion to Immune System Regulation and Diseases","volume":"25","author":"Li","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41581-019-0129-4","article-title":"Glycosylation in health and disease","volume":"15","author":"Reily","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/ni.3587","article-title":"Epithelial glycosylation in gut homeostasis and inflammation","volume":"17","author":"Goto","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1002\/art.38711","article-title":"Inhibition of fucosylation reshapes inflammatory macrophages and suppresses type II collagen-induced arthritis","volume":"66","author":"Li","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1136\/annrheumdis-2013-204814","article-title":"A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K\/BxN arthritis","volume":"74","author":"Amin","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/prca.200900150","article-title":"Glycosylation of liver acute-phase proteins in pancreatic cancer and chronic pancreatitis","volume":"4","author":"Sarrats","year":"2010","journal-title":"Proteom. Clin. Appl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1007\/s00535-011-0425-7","article-title":"Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn\u2019s disease","volume":"46","author":"Miyoshi","year":"2011","journal-title":"J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s12016-014-8423-1","article-title":"Fucosyltransferase 2: A genetic risk factor for primary sclerosing cholangitis and Crohn\u2019s disease--a comprehensive review","volume":"48","author":"Maroni","year":"2015","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1023\/A:1012412908983","article-title":"Increased alpha3-fucosylation of alpha1-acid glycoprotein in Type I diabetic patients is related to vascular function","volume":"18","author":"Poland","year":"2001","journal-title":"Glycoconj. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.jaci.2019.05.010","article-title":"Fucosyltransferase 2 induces lung epithelial fucosylation and exacerbates house dust mite-induced airway inflammation","volume":"144","author":"Saku","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Loong, J.H., Wong, T.L., Tong, M., Sharma, R., Zhou, L., Ng, K.Y., Yu, H.J., Li, C.H., Man, K., and Lo, C.M. (2021). Glucose deprivation induced aberrant FUT1-mediated fucosylation drives cancer stemness in hepatocellular carcinoma. J. Clin. Investig.","DOI":"10.1172\/JCI143377"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/bs.pmbts.2019.01.002","article-title":"Fucosylation in cancer biology and its clinical applications","volume":"162","author":"Shan","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrc3982","article-title":"Glycosylation in cancer: Mechanisms and clinical implications","volume":"15","author":"Pinho","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41419-020-2489-x","article-title":"FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress","volume":"11","author":"Kim","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/BST20170408","article-title":"Glycosylation pathways at the ocular surface","volume":"46","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S1542-0124(12)70213-6","article-title":"Structure and biological roles of mucin-type O-glycans at the ocular surface","volume":"8","author":"Argueso","year":"2010","journal-title":"Ocul. Surf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.carres.2018.10.004","article-title":"Glycosylation pathways of human corneal and conjunctival epithelial cell mucins","volume":"470","author":"Brockhausen","year":"2018","journal-title":"Carbohydr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10719-008-9136-6","article-title":"Glycan structures of ocular surface mucins in man, rabbit and dog display species differences","volume":"25","author":"Royle","year":"2008","journal-title":"Glycoconj. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1167\/iovs.09-3563","article-title":"Mucin-type O-glycans in tears of normal subjects and patients with non-Sjogren\u2019s dry eye","volume":"50","author":"Mantelli","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/00003226-198503000-00003","article-title":"Expression of ABO blood group, hematopoietic, and other cell-specific antigens by cells in the human cornea","volume":"4","author":"Treseler","year":"1985","journal-title":"Cornea"},{"key":"ref_21","first-page":"1184","article-title":"Expression of mucin peptide and blood group ABH- and Lewis-related carbohydrate antigens in normal human conjunctiva","volume":"35","author":"Garcher","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0379-0738(94)01630-N","article-title":"ABH and Lewis immunohistochemistry of the human eye","volume":"71","author":"Pedal","year":"1995","journal-title":"Forensic. Sci. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/02713689808951238","article-title":"Expression of blood group antigens A and\/or B in diseased corneas","volume":"17","author":"Ardjomand","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/cei.12759","article-title":"Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease","volume":"184","author":"Guzman","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_25","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","journal-title":"Ophthalmology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41R","DOI":"10.1093\/glycob\/cwg054","article-title":"Fucose: Biosynthesis and biological function in mammals","volume":"13","author":"Becker","year":"2003","journal-title":"Glycobiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158r","DOI":"10.1093\/glycob\/cwl040","article-title":"Fucosylation in prokaryotes and eukaryotes","volume":"16","author":"Ma","year":"2006","journal-title":"Glycobiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nature13823","article-title":"Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness","volume":"514","author":"Pickard","year":"2014","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fonc.2018.00039","article-title":"Fucosylated Antigens in Cancer: An Alliance toward Tumor Progression, Metastasis, and Resistance to Chemotherapy","volume":"8","author":"Blanas","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1471-4159.1990.tb13293.x","article-title":"Effects of the amnesic agent 2-deoxygalactose on incorporation of fucose into chick brain glycoproteins","volume":"54","author":"Bullock","year":"1990","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1073\/pnas.0503381102","article-title":"Protein fucosylation regulates synapsin Ia\/Ib expression and neuronal morphology in primary hippocampal neurons","volume":"103","author":"Murrey","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1254009","DOI":"10.1126\/science.1254009","article-title":"Innate lymphoid cells regulate intestinal epithelial cell glycosylation","volume":"345","author":"Goto","year":"2014","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25575","DOI":"10.1038\/srep25575","article-title":"Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding","volume":"6","author":"Rossez","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev.biochem.73.011303.074043","article-title":"Role of glycosylation in development","volume":"73","author":"Haltiwanger","year":"2004","journal-title":"Annu. Rev. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3892\/ol_00000064","article-title":"\u03b1(1,2)fucosylation in human colorectal carcinoma","volume":"1","year":"2010","journal-title":"Oncol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.2353\/ajpath.2007.070388","article-title":"Autoimmune dacryoadenitis of NOD\/LtJ mice and its subsequent effects on tear protein composition","volume":"171","author":"Doyle","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1136\/bjophthalmol-2012-302402","article-title":"Influence of single-fraction Gamma-Knife radiosurgery on ocular surface and tear function in choroidal melanoma patients","volume":"97","author":"Schneider","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yoon, C.H., Ryu, J.S., Hwang, H.S., and Kim, M.K. (2020). Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL\/6 Male Mouse Model. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114169"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/mt.2014.159","article-title":"Mesenchymal stem\/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye","volume":"23","author":"Lee","year":"2015","journal-title":"Mol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:33:49Z","timestamp":1760164429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/15\/7863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":39,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22157863"],"URL":"https:\/\/doi.org\/10.3390\/ijms22157863","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,23]]}}}