Topical Hepatocyte Growth Factor Accelerates Wound Healing and Inhibits Scarring in Experimental Corneal Injury

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Abstract
Purpose: The aim of this study was to compare the rates of healing, scar formation, and regression of preexisting scars using topical murine hepatocyte growth factor (mHGF), recombinant human deleted HGF (dHGF), murine nerve growth factor (mNGF), and phosphate-buffered saline (PBS). Methods: Mechanical corneal epithelial and stromal injury was induced in C57BL/6 mice. Five groups of mice were studied in each of phase I (wound healing and scar formation) and phase II (regression of preexisting scars). Each group received topical 0.1% mHGF, 0.1% dHGF, 0.2% dHGF, 0.1% mNGF, or PBS. In phase I, animals were dosed 4 times/day (QID) on days 0 to 7. In phase II, a corneal injury was induced, and no treatment was administered for 10 days to allow scar formation. Mice with scars were then dosed QID on days 11 to 21. Ocular assessments included slit-lamp photography (phase I and II) and fluorescein staining (phase I). Results: In phase I, eyes treated with mHGF exhibited significantly faster epithelial healing and decreased scar formation compared with both mNGF-treated and PBS-treated eyes 7 days after treatment. Consistent with that seen in mHGF-treated eyes, 0.1% and 0.2% dHGF-treated eyes each showed significantly faster epithelial healing compared with PBS-treated eyes. Scars formed in dHGF-treated eyes were also significantly smaller than PBS-treated eyes 7 days after treatment. In phase II, both mHGF-treated and dHGF-treated eyes showed a significant decrease in the size of preexisting scars compared with PBS-treated eyes. Conclusions: Topical HGF significantly accelerates corneal wound healing, reduces scar formation, and can reverse preexisting scars.

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