Losartan Inhibition of Myofibroblast Generation and Late Haze (Scarring Fibrosis) After PRK in Rabbits

Abstract

Purpose: To study the effect of topical losartan compared to vehicle on the generation of myofibroblasts and development of late haze scarring fibrosis after photorefractive keratectomy (PRK) in rabbits. Methods: Twelve rabbits had −9.00 diopter (D) PRK in one eye followed by 50 µL of topical 0.2 mg/mL losartan or 50 µL of vehicle six times per day for 1 month. Standardized slit-lamp photographs were obtained prior to death. Duplex immunohistochemistry was performed on cryofixed corneas for myofibroblast marker alpha-smooth muscle actin (α-SMA) and keratocyte marker keratocan or collagen type IV and transforming growth factor (TGF)-β1. ImageJ software (National Institutes of Health) was used for quantitation. Results: Topical losartan compared to vehicle significantly decreased corneal opacity ( P = .04) and anterior stromal myofibroblast generation ( P = .01) at 1 month after PRK. Topical losartan compared to vehicle also decreased anterior stromal non-basement membrane collagen type IV at 1 month after PRK ( P = .004). Conclusions: Topical angiotensin converting enzyme II receptor inhibitor losartan, a known inhibitor of TGF-β signaling, decreased late haze scarring fibrosis and myofibroblast generation after −9.00 D PRK in rabbits compared to vehicle. It also decreases TGF-β–modulated, corneal fibroblast-produced, non-basement membrane stromal collagen type IV—likely also through inhibition of TGF-β signaling. [ J Refract Surg . 2022;38(12):820–829.]