[Promotion of corneal epithelial wound healing with a tetrapeptide (SSSR) derived from insulin-like growth factor-1]

We have shown that the combination of insulin-like growth factor(IGF)-1 and substance P(SP) synergistically facilitates corneal wound healing. The carboxyl terminal four amino acids of SP(FGLM-amide) are sufficient for this synergism. The current study was conducted to investigate the minimal sequence of IGF-1 that is required for such synergism with SP or FGLM-amide. The effects of IGF-l--derived peptides on corneal epithelial migration were evaluated with a rabbit corneal organ-culture system. A tetrapeptide (SSSR) derived from the C domain of IGF-1 was sufficient for the synergistic promotion with FGLM-amide both of corneal epithelial migration in vitro and of wound closure in vivo. The activity of the SSSR peptide was sequence specific and its potency was similar to that of IGF-1. It was devoid, however, of both the mitogenic action of IGF-1 and the ability of the full-length molecule to induce neovascularization. Clinical application of the SSSR peptide would be expected to be free of potentially deleterious side effects associated with treatment with full-length IGF-1. Local administration of SSSR and FGLM-amide is thus a potential new strategy for the treatment of persistent corneal epithelial defects associated with neurotrophic keratopathy.