SYNERGISTIC EFFECTS OF SUBSTANCE-P WITH INSULIN-LIKE GROWTH-FACTOR-I ON EPITHELIAL MIGRATION OF THE CORNEA

We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP o r IGF-1 alone did not affect epithelial migration, while the combinati on of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelia l migration were nulled by the addition of a SP antagonist or enkephal inase. Among neurotransmitters (vasoactive intestinal peptide, calcito nin gene-related peptide, acethylcholine chloride, norepinephrine, ser otonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisi n, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 di d not affect the incorporation of H-3-thymidine into corneal epithelia l cells. The attachment of the corneal epithelial cells to fibronectin , collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not aff ect the attachment of the cells to these extracellular matrix proteins . An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, sugges ting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance o f the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors. (C) 1996 Wiley-Liss, Inc.