Abstract
Purpose: :
Lacritin is a stable, novel, naturally occurring human tear glycoprotein that promotes tear secretion in vitro and in vivo. Lacritin also increases the number of subconfluent (but not confluent) cultured human corneal epithelial cells suggesting that it may regulate the normal renewal of lacrimal tissue. In this study, duration, efficacy and tolerability of increasing doses of lacritin on tear production were studied. Lacritin was also compared to cyclosporine (Restasis®), or C-25 (inactive lacritin construct).
Methods: :
Lacritin (1, 10 or 50 µg/ml), cyclosporine (0.05%) or inactive C-25 lacritin (10 µg/ml) were administered bilaterally to New Zealand white rabbits three times daily for 14d (n=4/group). The treatment period was followed by a 7 d washout period where the rabbits were not treated. Bilateral tear production was measured at baseline and after washout. To ensure unstimulated tear production, proparacaine (0.5%) was applied 10 min prior to tear flow measurement. Slit-lamp examinations biomicroscopy was performed weekly. Data are expressed as a percentage of baseline (mean ± SEM).
Results: :
At the end of the washout, tear flow remained significantly greater than baseline in groups treated with 1, 10 and 50 µg/ml lacritin by 7±8%, 20±7% and 66±8% respectively (p<0.01, n=4). The 10 and 50 µg/ml doses were more effective than the 1 µg/ml (p<0.003). Lacritin (10 and 50 µg/ml) treatment was more effective than cyclosporine (12±3%, p<0.001). C-25 treatment did not increase tear production. All treatments were well tolerated as there were no significant toxic effects after slit-lamp examination. While mild corneal irritation was observed in all groups, iris irritation and discharge were noted only in the cyclosporine treated group.
Conclusions: :
Treatment with lacritin was well tolerated and longer lasting than cyclosporine. As a prosecretory mitogen, lacritin may regulate the normal renewal of lacrimal tissue. In this study lacritin stimulated tear flow was maintained for up to one week after cessation of therapy. The effect was dose dependent. Cyclosporine treatment caused irritation beyond the mild corneal irritation observed in all groups. Glycoproteins, such as lacritin, represent a new, unique therapeutic approach that may more closely address the pathophysiology of dry eye.
Keywords: cornea: tears/tear film/dry eye • drug toxicity/drug effects • ocular irritancy/toxicity testing