Investigating the effect of alpha-lipoic acid and retinoic acid eye drops on re-epithelialization, inflammation, and angiogenesis in a rabbit model of corneal wound healing through ICAM-1 and MMP-9 pathways.

Abstract

Corneal wound healing poses a significant clinical challenge involving cell death, migration, proliferation, and extracellular matrix remodeling. This study explores the effects of alpha-lipoic acid (LA) and retinoic acid (RA) eye drops on re-epithelialization, inflammation, and angiogenesis in a rabbit model of corneal wound healing, focusing on ICAM-1 (Intercellular Adhesion Molecule-1) and MMP-9 (Matrix Metalloroteinase-9) pathways. After an ocular examination of twelve New Zealand rabbits, a vertical linear wound was induced under anesthesia and confirmed by fluorescein staining. They were divided into four groups: control (isotonic saline), LA 1 %, RA 0.05 %, and a combination of both (RA + LA), administered twice daily for seven days. Clinical parameters and histological evaluations using H&E staining were conducted. Gene expression levels of ICAM-1, MMP-9, PDGFRα (Platelet-Derived Growth Factor Receptor α), and TGF-β (Transforming Growth Factor β) were measured by real-time PCR, with keratocan analyzed through immunohistochemistry. All treatment groups demonstrated significantly improved corneal healing compared to the control, with the RA + LA group showing the best histological repair. Real-time PCR results revealed significantly higher gene expression levels in the combination group than in the control and RA groups, and keratocan expression was significantly elevated in all treatment groups. In conclusion, LA and RA eye drops effectively enhance corneal healing by reducing inflammation and promoting re-epithelialization and angiogenesis, with the combined treatment showing the most pronounced effects.