Ocular Surface Mucins: Role in Dry Eye Disease
Ocular Surface Mucins: Role in Dry Eye Disease
Gary N. Foulks, MD, FACS
As research reveals more and more about the composition of the tear film, we are coming to realize that the tear film may be best conceptualized as a mucin gel. This view suggests that diminished or dysfunctional ocular surface mucins could play a key role in dry eye disease, and promising therapies that target this aspect of the disease support this idea.
Types of Ocular Surface Mucins
Consisting of both soluble and membrane-bound molecules, ocular surface mucins are highly glycosylated proteins that help structure the tear film by binding both to each other and to the aqueous component of the tear film. By helping to stabilize the tear film, mucins are essential for maintaining ocular surface health. In a normal eye, the concentration of ocular surface mucins is highest near the surface of the globe, and it gradually decreases as the tear/air interface is approached.
Within this gradient, different types of mucins occupy different positions and perform different functions:
Secreted mucins—such as MUC4 and MUC7—are produced by the lacrimal gland. These are the smallest mucin molecules in the tear film.
Gel-forming mucins—such as MUC5-AC—are secreted by the goblet cells of the conjunctiva. Like the secreted mucins, gel-forming mucins are dissolved in the tear film, but gel-forming mucins are larger and more interactive with other mucin molecules.
Membrane-associated mucins—such as MUC1 and MUC16—are even longer molecules that have an intracellular extension that anchors them to epithelial cells. These mucins play a key role in protecting the ocular surface, and when these mucins are absent or damaged, ocular surface staining results.
Role of Mucins in Dry Eye Disease
Because mucins are essential for maintaining a healthy tear film, a deficiency in mucin production or impaired mucin function may be an underlying cause of some cases of dry eye disease. “Mucin-deficient” dry eye disease occurs when certain types of mucins are absent from the ocular surface—either due to destruction of the goblet cells or due to changes in the expression of membrane-associated mucins on the corneal surface. The classic example of mucin-deficient dry eye disease is Stevens-Johnson syndrome, but vitamin A deficiency can also cause this condition.
Even when mucin dysfunction is not the primary etiology, it likely plays a role in most cases of advanced dry eye disease. Inflammatory processes can eradicate mucin-producing cells, and because inflammation typically plays a significant role in dry eye disease, long-term exposure to inflammatory mediators could damage mucin-producing cells and significantly impair normal mucin function.
Conclusion
Ocular surface mucins help structure the tear film, making mucins an essential component of a healthy ocular surface. Treatments that address mucin deficiency hold promise as a new avenue for treating dry eye disease. In particular, therapies such as secretagogues, topical cyclosporine, and mucomimetic artificial tears all show potential for addressing mucin deficiency.
Gary N. Foulks, MD, FACS, is the Arthur and Virginia Keeney professor of ophthalmology, University of Louisville, Louisville, KY, and is editor-in-chief of The Ocular Surface.
