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

Abstract

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 diameter Whatman #1 filter paper for 1 minute. Four corneas in each group were treated six times per day for 1 month with 50 µL of (1) 0.8 mg/mL losartan in balanced salt solution (BSS), (2) 1% prednisolone acetate, (3) combined 0.8 mg/mL losartan and 1% prednisolone acetate, or (4) BSS. Area of opacity and total opacity were analyzed in standardized slit-lamp photos with ImageJ. Corneas in both groups were cryofixed in Optimal cutting temperature (OCT) compound at 1 month after surgery, and immunohistochemistry was performed for alpha-smooth muscle actin (α-SMA) and keratocan or transforming growth factor β1 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 α-SMA area and intensity of staining per section and confined myofibroblasts 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.

• Authors: Lycia Pedral Sampaio, Guilherme S L Hilgert, Thomas Michael Shiju, Marcony R Santhiago, Steven E Wilson
• Journal: Translational vision science & technology (Transl Vis Sci Technol) Vol. 11 Issue 7 Pg. 9 (07 08 2022) ISSN: 2164-2591 [Electronic] United States
• PMID: 35819289 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adrenal Cortex Hormones
• Alkalies
• Collagen Type IV
• Losartan

Topics

• Adrenal Cortex Hormones (metabolism)
• Alkalies (metabolism, toxicity)
• Animals
• Burns, Chemical (complications, drug therapy, metabolism)
• Cicatrix (metabolism, pathology)
• Collagen Type IV (metabolism)
• Corneal Diseases (metabolism, pathology)
• Corneal Injuries (complications, drug therapy, metabolism)
• Fibrosis
• Losartan (metabolism, pharmacology, therapeutic use)
• Myofibroblasts (metabolism, pathology)
• Rabbits