TANAKA Toshiro Yamaguchi University School of Medicine, Assistant, 医学部, 助手 (30236608)
ENOKI Miho Yamaguchi University Hospital, Assistant, 医学部附属病院, 助手 (00274176)
KUMAGAI Naoki Yamaguchi University Hospital, Assistant Professor, 医学部附属病院, 講師 (20234510)
Our clinical experience that lost corneal sensation often induces persistent corneal epithelial defects or delay epitheliat wound healing suggested that sensory nerve system might play an important role in corneal epithelial wound healing. The ultimate purpose of the present study is to understand the pathology and to develop the new mode of treatment of neurotrophic keratopathy. For this end, we investigated the action mechanisms of the synergistic effects of substance P and ICF- 1 on corneal epithelium. Using an organ culture system of the cornea, we found that protein kinase C and tyrosine kinase, signal tansduction systems are involved in the synergistic effect of substance P and IGF- 1 . In addition, we found that a four amino acid sequence at the C-terminus of substance P, FGLM, was the minimum amino acid sequence for the synergistic effect with ICE-1 on corneal epithelial wound healing in vitro and in vivo. This synergism is expressed through the activation of integrin alpha5beta1, focal adhesion kinase, and paxillin system. In clinical situations, topical application of substance P + IGF-1 eye drops or FCLM + IGF-1 eye drops was effective in the treatment of severe neurotrophic keratopathy These results suggested that the treatment with eye drops containing substance P + ICF-1 or FCLM + IGF-1 may shed light on future approaches to the treatment of neurotrophic keratopathy.