Differential effect of rebamipide on transmembrane mucin biosynthesis in stratified ocular surface epithelial cells

Self Cite

Many studies have revealed that transmembrane mucins, large glycoproteins with heavily glycosylated glycans, are essential for maintaining ocular surface epithelium lubrication and wettability. Recent reports indicate that transmembrane mucins and galectin-3, a chimera type of galectin that binds b-galactoside in the glycan, play a crucial role in maintaining the epithelial glycocalyx barrier. This review summarizes current evidence regarding the role of galectin-3, the role of the three major transmembrane mucins (i.e., MUC1, MUC4, and MUC16), in the maintenance of ocular surface wettability and transcellular barrier. Pathological mechanisms of glycocalyx barrier disruption and epithelial surface wettability decreases in dry eye disease are also summarized. Lastly, new ophthalmic drugs that target transmembrane mucin are described.

Section: Rebamipide Ophthalmic Suspensionmentioning

confidence: 94%

The Ocular Surface Glycocalyx and its Alteration in Dry Eye Disease: A Review

Uchino

2018

Self Cite

“…However, to use the knowledge of dry eye mechanism in its treatment, an understanding of the pathologic processes of the disease is essential. The components of tears, such as clusterin, [10][11][12] mucin, [13][14][15][16] galectin, 17 and lipid, [18][19][20] also are important in understanding the homeostasis of the tear film and ocular surface. Recent studies have used inflammatory parameters, such as tear cytokines or dendritic cells (DCs) density as biomarkers to assess the efficacy of treatments.…”

mentioning

confidence: 99%

Inflammatory Response in Dry Eye

Yamaguchi

2018

184

120

PURPOSE. Dry eye is a major ocular pathology worldwide. Although dry eye is a multifactorial disease, recent studies have shown that chronic immunologic processes have a pivotal role in its pathogenesis, characterized by the infiltration of immune cells in the lacrimal glands, elevated levels of tear inflammatory cytokines, and increased density of immune cells in the cornea and conjunctiva. This review describes the recent advances in understanding the relationship between dry eye and inflammation. METHODS. This narrative review is based on searches of recent international literature using terms related to the immune response in dry eye, and includes clinical trials, animal experiments, and expert reviews. RESULTS. Although dry eye presents clinically as tear film instability associated with corneal/ conjunctival epithelial disorders, Meibomian gland dysfunction, and decreased visual function, recent laboratory and clinical studies have indicated inflammation in the lacrimal glands, Meibomian glands, conjunctiva, cornea, and aqueous tears. Furthermore, inflammation at these locations leads to conjunctival goblet cell apoptosis, corneal epithelial barrier disruption, and corneal nerve damage. These inflammatory outcomes can be exacerbated by intrinsic and extrinsic factors, such as aging, sex steroid hormone, autoimmune diseases, contact lens use, visual display terminals, and dry environment. CONCLUSIONS. Recent advances in dry eye research have revealed the inflammatory process and its pathogenesis, which has been proposed as an ''inflammatory vicious cycle'' of dry eye. Comprehensive assessment of dry eye based on inflammation will improve the selection of treatments and help break the inflammatory cycle in clinical settings.

“…RT-PCR and Western blot analysis showed that rebamipide increased membrane-associated mucins in mRNA and protein levels in the cultivated human corneal epithelial cells. 65,66 Uchino et al 66 reported that rebamipide increased MUC16 protein biosynthesis in the cultured human corneal epithelial, but not MUC1, MUC4, or MUC20. Two Japanese groups reported that rebamipide increased transmembrane electric resistance and protected TNF-a-induced disruption of the barrier function in cultured human corneal cells.…”

Section: New Therapeutic Approach For Treatment Of Dry Eyementioning

confidence: 99%

Secreted Mucins on the Ocular Surface

Hori

2018

Mucins, which play important roles on the ocular surface in wettability, lubrication, and barrier function, are classified into two categories: secreted mucins and membrane-associated mucins. The most important secreted mucin on the ocular surface is MUC5AC, which is secreted by the conjunctival goblet cells. In the human conjunctiva, goblet cells are present in higher concentrations in the fornix, inferior nasal bulbar, and the lid wiper on the lid margin. The number of conjunctival goblet cells and MUC5AC expression/secretion are decreased in a patient with dry eye. In Japan, drugs that stimulate mucin secretion or increase the number of conjunctival goblet cells are commercially available. A P2Y 2 receptor, diquafosol, stimulates tear fluid secretion from conjunctival epithelial cells and promotes mucin secretion from conjunctival goblet cells. Rebamipide was marketed originally as an oral therapeutic drug to treat gastritis in Japan. Topical rebamipide increases numbers of goblet cells in the bulbar conjunctiva and the lid wiper area of palpebral conjunctiva. Many researchers have reported decreases in the ocular surface mucin expression including MUC5AC secreted by goblet cells in patients with dry eye. However, it is unknown whether changes in mucin expression on the ocular surface cause or result from dry eye. Further study is needed to determine the true mechanism of dry eye disease.