Suppression of Conjunctival Scarring by Chymase Inhibitor in a Canine Symblepharon Model

Abstract

Purpose: To investigate the suppressive effects of a chymase inhibitor (CI) on conjunctival scarring in a canine model of symblepharon induced by alkali burns. Methods: Symblepharon models were made in beagle eyes. A cotton pad soaked in 1 N sodium hydroxide (NaOH) was placed in the conjunctival sac of each eye for 90 seconds, followed by washing the sac with 100 ml of physiological saline. Immediately post treatment, one eye drop (50 μl) including 1 mM-CI or the vehicle (CI-treated group and vehicle-treated group, respectively) was instilled in 5 eyes of 5 beagles once daily for 5 weeks. Fellow eyes were left untreated and served as the normal group. The severity of symblepharon was graded by macroscopic observation. After the eyes were enucleated, conjunctival and scleral tissue specimens were histologically evaluated. Results: Macroscopic observation revealed that symblepharon was induced in all NaOH-treated eyes, while symblepharon scores were significantly lower in the CI group than in the vehicle-treated group. Histological observation indicated a significant reduction in the adhered area in the CI-treated group compared to the vehicle-treated group. Immunohistochem- ical analysis demonstrated that vimentin-, α-smooth muscle actin-, chymase-, and angiotensin II-positive cells as well as mast cells increased in the vehicle-treated group compared to the normal group, whereas they were reduced in the CI-treated group. Conclusions: Our macroscopic and histological findings indicated that a multiple application of CI eye drops suppressed conjunctival scarring in a canine symblepharon model, suggesting that the topical application of CI may be a promising therapy for symblepharon.