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Updated: Jul 4, 2025
Ex Vivo and In Vivo Animal Models for Mechanical and Chemical Injuries of Corneal Epithelium
Published on: April 6, 2022
Topical Losartan Inhibition of Myofibroblast Generation in Rabbit Corneas With Acute Incisions
Valeria Villabona Martinez1, Barbara Araujo Lima Dutra1,2, Lycia Pedral Sampaio1,2
1Cole Eye Institute, Cleveland Clinic, Cleveland, OH; and.
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.
Insights
Topical losartan did not affect corneal incision closure but reduced myofibroblast generation around the injury site in rabbits. Further research is needed to understand its full impact on corneal wound healing.
Area of Science:
- Ophthalmology
- Wound Healing
- Pharmacology
Background:
- Corneal incisions require effective wound healing.
- Myofibroblasts play a role in corneal wound repair and scarring.
- Transforming growth factor beta (TGF-β) signaling is implicated in myofibroblast differentiation.
Purpose of the Study:
- To investigate the effect of topical losartan on the closure of deep central corneal incisions.
- To determine the impact of topical losartan on myofibroblast generation following corneal incisions in a rabbit model.
Main Methods:
- Deep radial corneal incisions were created in rabbits and treated with topical losartan or vehicle.
- Incision closure and opacity were assessed using slitlamp photography and ImageJ analysis.
- Myofibroblast density (α-SMA positive cells) surrounding incisions was quantified via immunohistochemistry (IHC).
Main Results:
- Topical losartan did not significantly alter the closure rate of corneal incisions.
- Losartan treatment led to a significant decrease in stromal myofibroblast density around the incisions.
- No significant difference in incision opacity was observed between losartan and vehicle groups at one month.
Conclusions:
- Topical losartan, an inhibitor of TGF-β signaling, does not impede deep corneal incision closure.
- Losartan effectively reduces myofibroblast generation adjacent to corneal incisions.
- The lack of effect on opacity suggests losartan may not influence all fibroblast populations involved in corneal scarring.
