Inhibition of Aberrant α(1,2)-Fucosylation at Ocular Surface Ameliorates Dry Eye Disease.

Chang Ho Yoon,Jung Hwa Ko,Joo Youn Oh,Jin Suk Ryu

doi:10.3390/ijms22157863

Abstract

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 α(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 α(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-γ+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.

Highlights

As fucoglycansglycans have multiple crucial roles in roles various biological processes, an increase sylated have multiple crucial in essential various essential biological processes, an in fucosylation or lack thereof has been implicated in pathological processes, including increase in fucosylation or lack thereof has been implicated in pathological processes, inblood transfusion reactions, sickle cell disease, infection, cancers and autoimmune discluding blood transfusion reactions, sickle cell disease, infection, cancers and autoimmune eases [1,2,3,4,5,6,7,8,9,10,11,12,13,28]
We found that the level of H2 antigen, one of terminally α(1,2)-fucosylated carbohydrate epitopes [29], was highly elevated at the ocular surface in α(1,2)-fucosylated carbohydrate epitopes [29], was highly elevated at the ocular surface
Tion inhibitor that blocks terminal α(1,2)-fucosylation [1,4,30,31], significantly ameliorated. These findings indicate the implication of aberrant fucosylation in dry eye disease (DED) pathogenesis and DED

Summary

Introduction

Fucosylation, a type of glycosylation, is one of the most common post-translational modifications involved in many basic cellular biological processes such as cell adhesion, recognition, development and host–microbe interactions [1,2]. The important roles of fucosylation in immune cell development and function have been uncovered [1,3]. Evidence is mounting that aberrant fucosylation plays a critical role in a number of inflammatory conditions such as rheumatoid arthritis [4,5], chronic pancreatitis [6], Crohn’s disease [7,8], type I diabetes [9] and allergic airway inflammation [10], as well as in cancer [11,12,13]

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Methods

Conclusion