Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury

Purpose: To evaluate the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits. Methods: Sixteen New Zealand White rabbits were included. Alkali injuries were produced using 1N sodium hydroxide on a 5-mm diameterWhatman #1 filter paper for 1 minute. Four corneas in each group were treated six times per day for 1 month with 50 mu L of (1) 0.2 mg/mL losartan in balanced salt solution (BSS), (2) 1% prednisolone acetate, (3) combined 0.2 mg/mL losartan and 1% prednisolone acetate, or (4) BSS. Area of opacity and total opacitywere analyzed in standardized slit-lamp photoswith ImageJ. Corneas in both groupswere cryofixed in Optimal cutting temperature (OCT) compound at 1 month after surgery, and immunohistochemistry was performed for alpha-smooth muscle actin (alpha-SMA) and keratocan or transforming growth factor beta 1 and collagen type IV with ImageJ quantitation. Results: Combined topical losartan and prednisolone acetate significantly decreased slit-lamp opacity area and intensity, as well as decreased stromal myofibroblast alpha-SMA area and intensity of staining per section and confinedmyofibroblasts to only the posterior stroma with repopulation of the anterior and mid-stroma with keratocan-positive keratocytes after 1 month of treatment. Corneal fibroblasts produced collagen type IV not associated with basement membranes, and this production was decreased by topical losartan. Conclusions: Combined topical losartan and prednisolone acetate decreased myofibroblast-associated fibrosis after corneal alkali burns that produced full-thickness injury, including corneal endothelial damage. Increased dosages and duration of treatment may further decrease scarring fibrosis. Translational Relevance: Topical losartan and prednisolone acetate decrease myofibroblast-mediated scarring fibrosis after corneal injury.

Automated summary

This study evaluated the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits. The results showed that the combined use of these two drugs significantly reduced opacity area and intensity, decreased myofibroblast area and staining intensity, and confined myofibroblasts to the posterior stroma while promoting repopulation of the anterior and mid-stroma with keratocan-positive keratocytes. Furthermore, topical losartan reduced the production of collagen type IV. These findings suggest that topical losartan and prednisolone acetate can effectively decrease myofibroblast-mediated scarring fibrosis after corneal injury.