Monday, January 7, 2008

Study: More on mucins

Well, I wish I could wave a magic wand over this to translate it to normal English. On the other hand, those of you who, like me, are interested in the mucin aspects of dry eye mostly know so much more about it than I do that I really don't have to bother :-) For those who don't know why they should care, mucin is the sticky substance on the surface of the cornea that makes tears adhere properly to the surface of the eye. With or without a good tear production or tear quality, the state of your mucin "layer" can make a big difference to your comfort and ocular surface health. That is why this area of research is so critical in the long-term.

Antiadhesive Character of Mucin O-glycans at the Apical Surface of Corneal Epithelial Cells.
Sumiyoshi M, Ricciuto J, Tisdale A, Gipson IK, Mantelli F, Argüeso P.
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):197-203.

PURPOSE: Prolonged contact of opposite mucosal surfaces, which occurs on the ocular surface, oral cavity, reproductive tract, and gut, requires a specialized apical cell surface that prevents adhesion. The purpose of this study was to evaluate the contribution of mucin O-glycans to the antiadhesive character of human corneal-limbal epithelial (HCLE) cells.
METHODS: Mucin O-glycan biosynthesis in HCLE cells was disrupted by metabolic interference with benzyl-alpha-GalNAc. The cell surface mucin MUC16 and its carbohydrate epitope H185 were detected by immunofluorescence and Western blot. HCLE cell surface features were assessed by field emission scanning electron microscopy. Cell-cell adhesion assays were performed under static conditions and in a parallel plate laminar flow chamber.
RESULTS: Benzyl-alpha-GalNAc disrupted the biosynthesis of O-glycans without affecting apomucin biosynthesis or cell surface morphology. Static adhesion assays showed that the apical surface of differentiated HCLE cells expressing MUC16 and H185 was more antiadhesive than undifferentiated HCLE cells, which lacked MUC16. Abrogation of mucin O-glycosylation in differentiated cultures with benzyl-alpha-GalNAc resulted in increased adhesion of applied corneal epithelial cells and corneal fibroblasts. The antiadhesive effect of mucin O-glycans was further demonstrated by fluorescence video microscopy in dynamic flow adhesion assays. Cationized ferritin labeling of the cell surface indicated that anionic repulsion did not contribute to the antiadhesive character of the apical surface.
CONCLUSIONS: These results indicate that epithelial O-glycans contribute to the antiadhesive properties of cell surface-associated mucins in corneal epithelial cells and suggest that alterations in mucin O-glycosylation are involved in the pathology of drying mucosal diseases (e.g., dry eye).

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