Topical Losartan Inhibition of Myofibroblast Generation in Rabbit Corneas With Acute Incisions

Abstract

Purpose: The purpose of this study was to study whether deep central corneal incisions close during topical losartan treatment and the effect of topical losartan on myofibroblast generation after incisions in rabbit corneas. Methods: Rabbits (12) had a 0.35-mm deep radial incision from the center of the cornea into the limbus in 1 eye that was approximated with a single 10-0 nylon suture 1 mm inside the limbus. The incision was treated with 50 μL of topical 0.8 mg/mL losartan or 50 μL of balanced salt solution vehicle 6 times per day for 1 month. Standardized slitlamp photographs of the central incisions were analyzed for opacity with ImageJ before euthanasia. Triplex IHC was performed on cryofixed corneas for myofibroblast marker alpha-smooth muscle actin, mesenchymal cell marker vimentin, and basement membrane marker laminin alpha-5. Stromal α-SMA–positive myofibroblasts surrounding the incisions were quantitated with ImageJ. Results: Topical losartan compared with vehicle did not affect closure of the radial incisions or the opacity that developed surrounding the incisions at 1 month after injury. Topical losartan compared with vehicle did significantly decrease the average density of stromal myofibroblasts surrounding the incisions. Conclusions: Topical losartan, a known inhibitor of transforming growth factor beta signaling, did not affect closure of deep corneal incisions. Losartan decreased myofibroblast generation surrounding nearly full-thickness radial corneal incisions compared with vehicle. The opacity at the incisions was not significantly affected by losartan—likely because corneal fibroblasts that develop in the stroma adjacent to the incisions were not changed by the losartan compared with the vehicle.