Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy.
OBJECTIVE
To investigate the effects of topical application of the combination of substance P (SP) and insulin-like growth factor (IGF)-1 on corneal epithelial barrier function and epithelial wound closure in rats with capsaicin-induced neurotrophic keratopathy.


METHODS
Neonatal rats were injected subcutaneously with a single dose of capsaicin to induce neurotrophic keratopathy. Corneal epithelial barrier function was evaluated with an anterior fluorophotometer. Tear fluid secretion was measured by the Schirmer test. Corneal epithelial wound healing was determined by measurement of the size of the epithelial defect after debridement of the entire epithelium. The combination of SP (1 mM) and IGF-1 (1 micro g/mL) in phosphate-buffered saline was administered in eye drops six times daily.


RESULTS
Corneal epithelial barrier function was impaired and corneal epithelial wound healing was delayed in rats injected with capsaicin. The application of eye drops containing the combination of SP and IGF-1 to capsaicin-injected rats resulted in a significant improvement in corneal epithelial barrier function compared with that apparent in capsaicin-injected animals that received eye drops containing vehicle alone. Such treatment with SP and IGF-1 also significantly increased the rate of corneal epithelial wound closure in capsaicin-injected animals.


CONCLUSIONS
Topical application of the combination of SP and IGF-1 improved both corneal epithelial barrier function and epithelial wound healing in an animal model of neurotrophic keratopathy.
Nakamura
Masatsugu
M
Ophthalmic Research Division, Santen Pharmaceutical Co. Ltd., Ikoma, Nara, Japan. nakamura@santen.co.jp
Kawahara
Megumi
M
Nakata
Katsuhiko
K
Nishida
Teruo
T
D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002211:Capsaicin / Q000633:toxicity; D003315:Cornea / Q000294:innervation / Q000502:physiology*; D003316:Corneal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000502:physiology; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D015590:Fluorophotometry; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009883:Ophthalmic Solutions; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000008:administration & dosage / Q000627:therapeutic use*; D013666:Tears / Q000378:metabolism; D020433:Trigeminal Nerve Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D009883:Ophthalmic Solutions; D013373:Substance P; D007334:Insulin-Like Growth Factor I; D002211:Capsaicin; D019793:Fluorescein