Abstract
Purpose: :
The pathophysiology of dry eye is multifactorial, but common to all etiologies is a decrease in both volume and quality of tear secretion. Lacritin is a natural protein component of tears and stimulates lacrimal cell growth. Lacritin is produced predominantly by lacrimal and salivary glands. Based on these properties, we hypothesize that lacritin will stimulate production of normal tears without toxic effects.
Methods: :
White New Zealand rabbits (n = 5) were treated topically 3x/day with 50 µl lacritin (150 µg/ml) in the right eye (OD) and with vehicle alone in the left eye (OS, control) for 4 wk. Tears were collected weekly 30 min after lacritin application and assayed for pH, electrolyte, and protein content. Tear flow (mm) using Schirmer strips, and a semiquantitative analysis of ocular toxicity using slit lamp biomicroscopy examinations (SLE), were evaluated weekly. Lissamine Green (LG) and Rose Bengal (RB) staining were performed at the end of the study.
Results: :
Lacritin increased tear flow by 8–11 mm but vehicle increased flow only 2–4 mm (p<0.001). There was no significant difference in pH, protein or sodium content between OD and OS. Potassium was slightly higher in treated eyes, but the difference was significant only at wk 4 (p = 0.013). By SLE, no conjunctival congestion, chemosis, discharge, or photophobia were observed in 3/5 rabbits. Mild irritation in both eyes was noted in the other 2 rabbits after 1 wk treatment, but no irritation was noted in either eye at wk 3 or 4. By SLE, there was no conjunctiva and cornea staining with either LG or RB.
Conclusions: :
Topical application of lacritin effectively stimulated tear flow over a 4 wk treatment period. The increase in tear flow did not significantly change throughout the 4 wk, suggesting that lacritin’s pharmacological effects are not attenuated during extended treatment. Lacritin had minimal effect on tear composition. Lack of Rose Bengal staining suggested normal lipid composition. Although there was some mild, transient ocular irritation, this was unlikely a result of lacritin application, as the irritation was present in both lacritin and vehicle–treated eyes. Thus, based on lacritin’s ability to increase tear flow and non–toxic effects for an extended treatment period, lacritin has shown significant potential as a novel therapeutic agent for the future medical treatment of dry eye.
Keywords: pharmacology • lacrimal gland • cornea: tears/tear film/dry eye