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(Investigative Ophthalmology and Visual Science. 2005;46:833-839.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0775
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Sensitizing Effect of Substance P on Corneal Epithelial Migration Induced by IGF-1, Fibronectin, or Interleukin-6

Naoyuki Yamada,1,2 Ryoji Yanai,1,2 Makoto Inui,2 and Teruo Nishida1

1From the Departments of Biomolecular Recognition and Ophthalmology and 2Pharmacology, Yamaguchi University School of Medicine, Yamaguchi, Japan.

PURPOSE. Substance P (SP) is present in the sensory nerve fibers of the corneal epithelium. Various biological agents, including epidermal growth factor, fibronectin, interleukin-6, and the combination of SP and insulin-like growth factor (IGF)-1, promote the healing of corneal epithelial wounds. The role of SP in corneal epithelial migration was examined.

METHODS. The effects of various agents on corneal epithelial migration were investigated with the rabbit cornea in an organ culture system.

RESULTS. An SP-derived tetrapeptide, FGLM-amide, shifted the dose–response relations for the induction of corneal epithelial migration not only by an IGF-1–derived peptide (C-domain peptide) but also by fibronectin or interleukin-6 to lower concentrations. This action of SP was prevented by inhibitors of phospholipase C, of the inositol 1,4,5-trisphosphate receptor–mediated release of Ca2+ from intracellular stores, and of Ca2+- and calmodulin-dependent protein kinase II (CaM-PK II).

CONCLUSIONS. These results indicate that SP, acting at the neurokinin type 1 receptor, functions as an important modulator of corneal epithelial wound healing by activating CaM-PK II in epithelial cells and thereby sensitizing them to the induction of migration by various biological agents. They also provide important insight into a new strategy for the treatment of corneal wounds.




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