Promotion of Corneal Epithelial Wound Healing by the C Domain of Insulin-Like Growth Factor–1 in the Presence of Substance P

Abstract

Abstract: : Purpose: Insulin-like growth factor–1 (IGF-1) and substance P (SP) synergistically promote corneal epithelial migration in vitro and corneal epithelial wound healing in vivo. A tetrapeptide (FGLM-amide) derived from the carboxyl terminus of SP mimics this action of the full-length molecule. Although IGF-1 and insulin are similar in molecular structure, the synergistic effect of IGF-1 with SP is not mimicked by insulin. To determine which domain of IGF-1 is responsible for the synergistic action of this growth factor with SP or FGLM-amide on corneal epithelial migration, we examined the effects of peptides corresponding to the C and D domains which exhibit no sequence homology to those of insulin. Methods: The effects of IGF-1–derived peptides on corneal epithelial migration were measured with the rabbit cornea in an organ culture system. Corneal epithelial wound closure in vivo was evaluated in rabbits after epithelial debridement with n-heptanol. Results: The C domain peptide of IGF-1 significantly increased the extent of corneal epithelial migration in vitro in the presence of FGLM-amide to an extent similar to that observed with full-length IGF-1; in contrast, the D domain peptide had no such effect. Point mutation of serine-34 of the C domain of IGF-1 abolished the synergistic effect with FGLM-amide. The administration of eye drops containing the C domain peptide and FGLM-amide also significantly promoted corneal epithelial wound closure in vivo. Conclusion: The C domain of IGF-1, for which a biological function has not been known, is essential for the synergistic effect of IGF-1 with SP on corneal epithelial migration.

Keywords: cornea: basic science • wound healing • growth factors/growth factor receptors