Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1.
OBJECTIVE
The healing of corneal epithelial wounds is often delayed in individuals with diabetes. The effect of the combination of a substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine amide, or FGLM-NH(2)) and insulin-like growth factor-1 (IGF-1) on corneal epithelial wound healing was investigated in rats with streptozotocin-induced diabetes.


METHODS
The corneal epithelium of diabetic and non-diabetic rats was removed, and the animals were treated by the application of eye drops containing FGLM-NH(2) and IGF-1, or vehicle alone as a control, six times a day for 3 days. The area of the corneal epithelial wound was measured at various times up to 72 h after removal of the corneal epithelium.


RESULTS
The rate of corneal epithelial wound healing was slower in diabetic rats treated with vehicle than in non-diabetic rats. However, the rate of wound closure in diabetic rats treated with FGLM-NH(2) and IGF-1 was markedly increased compared with that in diabetic rats treated with vehicle. The wound healing process seemed similar in normal rats and in diabetic rats treated with FGLM-NH(2) and IGF-1.


CONCLUSIONS
The combination of FGLM-NH(2) and IGF-1 promotes corneal epithelial wound healing in diabetic rats, suggesting that such a treatment might prove effective in humans with diabetic keratopathy.
Nakamura
M
M
Ophthalmic Research Division, Santen Pharmaceutical Co. Ltd., 8916-16 Takayama-cho, Ikoma-shi, Nara 630-0101, Japan. nakamuram@santen.co.jp
Kawahara
M
M
Morishige
N
N
Chikama
T
T
Nakata
K
K
Nishida
T
T
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D019573:Epithelium, Corneal / Q000293:injuries*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014945:Wound Healing / Q000187:drug effects*
D001786:Blood Glucose; D009842:Oligopeptides; C112946:phenylalanyl-glycyl-leucyl-methioninamide; D007334:Insulin-Like Growth Factor I