discovering dry eye
MUC 1 and Other Important Components of the Mucus Layer
BY BARBARA CAFFERY, OD, MS, FAAO
Allergy season has arrived in the Northern Hemisphere. Clinicians will hear stories of excess mucus and ocular itching. Contact lenses develop coatings on the surface that we believe are mucus based. Patients complain of stringy secretions and "sleep" in their eyes in the morning. What causes this mucus to present itself?
Building Blocks of the Tear Film
The tear film is approximately 40nm thick. Mucus within the tear film provides the major structural component and may contribute up to 30nm of its thickness. The mucus layer is thicker at the apical layer of the epithelial cells and thinnest at the surface of the tear film.
Mucins are highly glycosylated proteins that are at least 50 percent carbohydrate by mass. At least eight to nine mucins exist in human tissue. They are designated as MUC1 to 4, 5AC, 5B and 6 to 8. Some mucin categories are described based on their structural features. MUC1 is the most studied mucin. It has a membrane-spanning sequence and a long extra cellular domain. This long tail extends 200 to 500nm through the glycocalyx of the cell into the tear film.
There are four gel-forming mucins. MUCs 2, 5AC, 5B and 6 are very large molecules that contribute to the gel-forming aspect of the tear film. They are usually the major structural components on all wet epithelial mucosal layers of the body. The trachea expresses MUC 2, 5AC and 5B; the stomach expresses 5AC and 6; the colon expresses 2, 3 and 5B; and the endocervix expresses 5AC, 5B and 6. MUC 7 is a small, secreted, non-gel-forming mucin found in the salivary gland.
Goblet cells of the conjunctiva provide the major mucins that assemble the tear film. The stratified epithelium of the conjunctiva and cornea, the lacrimal gland and, by inference, the accessory lacrimal glands also contribute. Ocular surface epithelia express at least three mucin genes. Corneal and conjunctival epithelia express the transmembrane mucin MUC1. MUC1 serves as an anti-adhesive agent, preventing ocular surface adhesion of sloughed cells, debris and pathogens. It may also prevent the tear film's mucus coat from adhering to the ocular surface. It likely promotes the non-adhesion of the lid to the ocular surface, promoting smooth action of the lid in resurfacing the ocular surface with new tears.
MUC5AC is clearly mapped in conjunctival goblet cells. It is the major gel-forming mucin on the surface of the eye.
Stimulating Mucus Production
It is likely that there is a basal creation and secretion of mucus onto the eye's surface, possibly because of a neurological stimulus. Morphological evidence suggests that rat conjunctival epithelial cells secrete mucin in response to VIP, serotonin or adrenergic agonists. Cholinomimetric drugs have also been shown to stimulate conjunctival mucin secretion, but little is known of the mechanism.
In several disease states the sub-surface vesicles found within the epithelial cells that contain mucus change considerably. The number of vesicles increases in vernal conjunctivitis, in patients wearing PMMA prostheses and in contact lens wearers. Patients with keratoconjunctivitis sicca have fewer vesicles present. The stimulus for the change of vesicle presence is not understood. Perhaps there are mechanical, chemical and neurological stimuli that vary in importance with each disease state.
Whatever the mechanism, mucus is a vital component of the ocular surface. Its absence destroys the health of the epithelial cells, and its excess causes disturbances of the ocular surface and discomfort.
Dr. Caffery has practiced optometry in Toronto, Canada, in a group setting dedicated to contact lens and tear film research since 1977.