Character of ocular surface mucins and their alteration in dry eye disease.

At the ocular surface, three types of mucins are present. The large gel-forming mucin MUC5AC is expressed by conjunctival goblet cells. Some cells of the lacrimal gland acini express the small soluble mucin MUC7. The corneal and conjunctival epithelia express the membrane-associated mucins MUCs 1, 4, and 16. With the characterization of the mucin gene repertoire of the ocular surface epithelia, studies of the function of specific mucins, their gene regulation, and their alteration in ocular surface disease have begun. Current information suggests that all the mucins are hydrophilic and play a role in maintenance of water on the surface of the eye. The large secreted mucins represent the "janitorial service" that moves over the surface of the eye to wrap up and remove debris. The membrane-associated mucins form the glycocalyx, which provides a continuous barrier across the surface of the eye that prevents pathogen penetrance and has signaling capabilities that influence epithelial activity. Factors regulating mucin gene expression include retinoic acid, serum, and dexamethasone. Alteration in both secreted and membrane-associated mucins occur in drying ocular surface diseases. In Sjogren syndrome, MUC5AC expression is reduced, and in non-Sjogren dry eye, glycosylation of MUC16 appears to be altered. The pattern of expression of enzymes that glycosylate mucins is altered in ocular cicatricial pemphigoid. Therapies being evaluated for dry eye, including cyclosporine A, P2Y2 agonists, gefarnate, 15-(S)-HETE, and corticosteroids, may be efficacious due to their effect on mucin gene expression and secretion.