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Therapeutic Effects of Epidermal Growth Factor on Benzalkonium Chloride-Induced Dry Eye in a Mouse Model.
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 (3ng/day) on BAC-induced dry eye model. The following clinical indications of dry eye were evaluated on D2, 4 and 6: tear break-up time (BUT), corneal fluorescein staining, inflammatory index and tear volume. Global specimens were collected on D6 and then the following examinations were performed: histological 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.
Results
EGF resulted in longer BUTs on D2 and D6, lower fluorescein staining scores on D4 and D6 while no significant changes in inflammatory index or tear volume. EGF induced higher EGFR expression in corneal tissues by immunofluorescent staining and Western blot. EGF also up-regulated 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. Our results indicated that EGF had the potential in the clinical treatment of dry eye.
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 (3ng/day) on BAC-induced dry eye model. The following clinical indications of dry eye were evaluated on D2, 4 and 6: tear break-up time (BUT), corneal fluorescein staining, inflammatory index and tear volume. Global specimens were collected on D6 and then the following examinations were performed: histological 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.
Results
EGF resulted in longer BUTs on D2 and D6, lower fluorescein staining scores on D4 and D6 while no significant changes in inflammatory index or tear volume. EGF induced higher EGFR expression in corneal tissues by immunofluorescent staining and Western blot. EGF also up-regulated 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. Our results indicated that EGF had the potential in the clinical treatment of dry eye.
Xiao X, He H, Lin Z, Luo P, He H, Zhou T, Zhou Y, Liu Z.
. Eye Institute of Xiamen University, Xiamen, P.R.China.