Altered Mucin and Glycoprotein Expression in Dry Eye Disease.
OBJECTIVE
Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye.


METHODS
We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye.


RESULTS
Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1.


CONCLUSIONS
Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.
*PhD †OD, PhD Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California (both authors); Departments of Anatomy and Ophthalmology, University of California, San Francisco, San Francisco, California (NAMc); and School of Optometry and Vision Science Graduate Group, University of California, Berkeley, California (NAMc).
Denise N
DN
Stephens
Nancy A
NA
McNamara
D000818:Animals; D015352:Dry Eye Syndromes / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D013666:Tears / Q000737:chemistry
D008562:Membrane Glycoproteins; D009077:Mucins