Therapeutic Effects of Epidermal Growth Factor on Benzalkonium Chloride-Induced Dry Eye in a Mouse Model

National Basic Research Program of China (Project 973) [2011CB504606]; National Natural Science Foundation of China [30931160432, 30872810]; Technological innovation platform program of Fujian Province, China [2009J1013]; Cross-strait technological platform of Chinese medicine [3502Z20100006]; Watsin Company (Shenzhen, China)PURPOSE. To investigate the therapeutic effects and possible mechanisms of epidermal growth factor (EGF) on the mouse dry eye model induced by benzalkonium chloride (BAC). METHODS. The eye drop containing EGF was topically administered (3 ng per day) on a BAC-induced dry eye model. The following clinical indications of dry eye were evaluated on Days 2, 4, and 6: tear break-up time (BUT), corneal fluorescein staining, inflammatory index, and tear volume. Global specimens were collected on Day 6 and then the following examinations were performed: histologic investigation, TUNEL assay to measure the dead cells, periodic acid-schiff (PAS) assay to detect goblet cells, and immunostaining of antibodies of Ki-67, EGF receptor (EGFR), and MUC1 in the corneas. The levels of EGFR and p-ERK of the corneas were also measured by Western blot analysis. RESULTS. EGF resulted in longer BUTs on Days 2 and 6, lower fluorescein staining scores on Days 4 and 6, while no significant changes in inflammatory index or tear volume. EGF induced higher EGFR expression in corneal tissues by immunofluorescent staining and Western blot analysis. EGF also upregulated p-ERK, increased Ki-67 positive cells, and decreased TUNEL positive cells. In addition, EGF significantly increased the goblet cells number and MUC1 expression in the epithelium. CONCLUSIONS. Topical application of EGF presented clinical improvements on dry eye by stabilizing the tear film and maintaining the integrity of epithelium. The results indicate that EGF has potential as a therapeutic agent in clinical treatment of dry eye. (Invest Ophthalmol Vis Sci. 2012;53:191-197) DOI:10.1167/iovs.11-855