Abstract
Purpose :
To study the effect of topical losartan compared to vehicle on the generation of myofibroblasts and late haze scarring fibrosis after surface blast injury simulating irregular phototherapeutic keratectomy (PTK).
Methods :
Twelve female New Zealand White rabbits underwent excimer laser ablation over a fine mesh screen onto the central corneal stromal surface with 100 pulses of PTK to 25μm depth. Eyes were treated with 50 μL of topical 0.8 mg/mL Losartan or 50 μL of vehicle six times a day for 6 weeks. Standardized slit lamp photographs were taken at two, four and six weeks after injury. Each cornea was evaluated at 6 weeks after injury using immunohistochemistry for keratocan (keratocyte marker), vimentin (mesenchymal cell marker), and alpha-smooth muscle actin (a-SMA, myofibroblast marker) on cryofixed corneas
Results :
One losartan-treated rabbit was excluded from statistical comparisons because it developed an epithelial defect four weeks after irregular PTK. Topical losartan compared to vehicle significantly decreased anterior stromal myofibroblast generation (P=0.009) and trended towards a decrease in central corneal opacity (P=0.13) at six weeks after irregular PTK.
Conclusions :
Topical angiotensin II receptor blocker (ARB) losartan, a known inhibitor of TGF-b signaling, decreased stromal myofibroblast generation and trended towards decreasing fibrotic opacity after severe scar producing irregular PTK in rabbits compared to vehicle. Scarring opacity would likely have decreased further with longer treatment due to ongoing corneal fibroblast activity. Topical losartan is likely to be effective in reducing and preventing corneal scarring fibrosis produced by corneal infection, trauma, surgery and some diseases
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.