MUCIN GENES EXPRESSED BY THE OCULAR SURFACE EPITHELIUM

Mucins are the glycoproteins which form the viscous, gel-like mucus la yer of the tear film. Molecular characterization of mucins has been sl ow due to their heavy glycosylation and high molecular weight, but rec ent cloning of human gut and trachea, mammary gland, and salivary glan d mucins has begun to shed light on the primary structure of these imp ortant protective molecules. To date nine human mucin genes, designate d MUC1-8, have been cloned. The presence in the protein backbone of ta ndem 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 ea ch tandem repeat varies with each mucin. Numbers of amino acids per re peat vary from 169 (MUC6) to 8 (MUC5AC). Until recently little has bee n known regarding the expression of these genes by the ocular surface epithelium. This review summarizes recent work from our laboratory aim ed at determining the molecular character of mucins expressed by conju nctival and corneal epithelium. Using northern blot analysis and in si tu hybridization techniques, we have demonstrated that the stratified epithelium of both cornea and conjunctiva express the transmembrane mu cin, MUC1. This widely expressed mucin is the best characterized of th e 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 be tween mucin molecules. Conjunctival stratified epithelium expresses MU C4, a relatively uncharacterized mucin, whose function is not known. A re there additional and/or unique mucins expressed by the ocular surfa ce epithelium? We summarize our recent work on characterization of a m ucin isolated from rat and human corneal epithelium. Antibodies to the se mucins localize to the glycocalyx of the corneal epithelial apical cells. Since MUC1 appears to be the only one of the cloned mucins expr essed by the corneal epithelium. it is a candidate for comparison to o ur mucin isolate. Current efforts are directed toward this comparison. Identification of mucin genes expressed by the ocular surface epithel ium opens many new avenues for investigation into expression, regulati on, and glycosylation of mucins in ocular surface pathologies and into the specific character of these molecules which enhance protection fr om pathogen invasion. Copyright (C) 1996 Elsevier Science Ltd.