Mucin genes expressed by the ocular surface Epithelium

Abstract

Mucins are the glycoproteins which form the viscous, gel-like mucus layer of the tear film. Molecular characterization of mucins has been slow due to their heavy glycosylation and high molecular weight, but recent cloning of human gut and trachea, mammary gland, and salivary gland mucins has begun to shed light on the primary structure of these important protective molecules. To date nine human mucin genes, designated MUCI-8, have been cloned. The presence in the protein backbone of tandem repeats of series of amino acids rich in serine and/or threonine is a feature common to all. Numbers and sequences of amino acids in each tandem repeat varies with each mucin. Numbers of amino acids per repeat vary from 169 (MUC6) to 8 (MUC5AC). Until recently little has been known regarding the expression of these genes by the ocular surface epithelium. This review summarizes recent work from our laboratory aimed at determining the molecular character of mucins expressed by conjunctival and corneal epithelium. Using northern blot analysis and in situ hybridization techniques, we have demonstrated that the stratified epithelium of both cornea and conjunctiva express the transmembrane mucin, MUC1. This widely expressed mucin is the best characterized of the cloned mucins. Using similar methodologies we demonstrated that the conjunctival goblet cell expresses MUC5AC, a gel-forming mucin, which has a cysteine-rich domain responsible for the disulfhydryl bonding between mucin molecules. Conjunctival stratified epithelium expresses MUC4, a relatively uncharacterized mucin, whose function is not known. Are there additional and/or unique mucins expressed by the ocular surface epithelium? We summarize our recent work on characterization of a mucin isolated from rat and human corneal epithelium. Antibodies to these mucins localize to the glycocalyx of the corneal epithelial apical cells. Since MUCI appears to be the only one of the cloned mucins expressed by the corneal epithelium, it is a candidate for comparison to our mucin isolate. Current efforts are directed toward this comparison. Identification of mucin genes expressed by the ocular surface epithelium opens many new avenues for investigation into expression, regulation, and glycosylation of mucins in ocular surface pathologies and into the specific character of these molecules which enhance protection from pathogen invasion.