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

Abstract

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. 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. 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). 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.].