Effect of lacritin, a novel glycoprotein, on ocular surface and tear film integrity

Abstract

AbstractPurpose Dry eye is extremely common and debilitating. Treatment options are palliative at best and do not address the underlying pathology. Lacritin, a newly discovered glycoprotein, is secreted naturally in human tears by the lacrimal gland. Human recombinant lacritin stimulated tear secretion in normal rabbits and is well tolerated, leading us to hypothesize that topical application of lacritin will not adversely affect ocular surface and tear film integrity.Methods We compared full length lacritin construct with cyclosporin (Restasis®), in terms of tear break up time (TBUT) and goblet cell density using impression cytology. Lacritin (10, 50 μg/ml), or cyclosporin (0.05%), were administered bilaterally to New Zealand white rabbits three times daily for 14d (n=4/group).Results TBUT after lacritin (10 or 50 μg/ml) treatment was 12±2sec, which was similar to vehicle alone, but significantly decreased after cyclosporine treatment for 14d (6±3sec, p<0.001). Preliminary results indicate that goblet cell density decreased by 7±8% after cyclosporine but was not decreased after lacritin. No local irritant effects were noted by slit lamp examination after lacritin treatment, but redness and mild congestion were present in the cyclosporin group.Conclusion Thus, treatment with lacritin was better tolerated than cyclosporin. This data suggests that lacritin does not adversely ocular surface and tear film integrity when compared to cyclosporine. Evaluation with inflammatory markers, such as CD‐11c, is currently ongoing. Glycoproteins, such as, lacritin, represent a new, unique therapeutic approach that may more closely address the pathology of dry eye. Commercial interest