Optimal concentration of human epidermal growth factor (hEGF) for epithelial healing in experimental corneal alkali wounds.
OBJECTIVE
By using both in vivo and in vitro (organ-cultured) systems, the optimal concentrations of hEGF to enhance epithelial healing after alkali wounds were evaluated in the rabbit cornea.


METHODS
Alkali-injured corneas (pi = 5.5 mm, 1 N NaOH, 60 s) were treated with 0.01, 0.1, 1.0, 10 and 100 ng/ml hEGF for the in vitro study. The healing of epithelium and endothelium was determined at 1, 2, 3, 4, and 6 days after treatment. For the in vivo experiment, the eyes were treated with 2, 5, 10, and 50 microg/ml hEGF 3 times per day. The measurement of epithelial healing rate, transmission electron microscopy and immunohistochemical observation were performed after 7 days treatment.


RESULTS
In in vitro tests, hEGF enhanced the epithelial healing rates, showing a maximum enhancement at the concentration of 1.0 ng/ml, and endothelial healing was increased at 100 ng/ml. In in vivo studies, no significant difference was observed in the rates of epithelial healing between control and each hEGF-treated group. Among the tested concentrations, 5 microg/ml hEGF induced the most active proliferation of basal cells and 50 microg/ml hEGF remarkably produced a vascular ingrowth to the central wound area. The thickness of re-surfaced epithelium was increased by hEGF in a concentration-dependent manner.


CONCLUSIONS
The results of the present study indicate that a low concentration of hEGF may selectively enhance epithelial healing without affecting endothelial healing. The optimal concentration of hEGF for the stimulation of epithelial healing appears to be 5 microg/ml in rabbit corneal alkali wounds.
Kim
M J
MJ
Department of Ophthalmology, Mokdong Hospital, Ewha Women's University, 911-1 Mokdong, Yangcheon-ku, 158-056, Seoul, Korea.
Jun
R M
RM
Kim
W K
WK
Hann
H J
HJ
Chong
Y H
YH
Park
H Y
HY
Chung
J H
JH
D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D003316:Corneal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004728:Endothelium, Corneal / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005126:Eye Burns / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009924:Organ Culture Techniques; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits; D012972:Sodium Hydroxide; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D018809:Proliferating Cell Nuclear Antigen; D012972:Sodium Hydroxide; D004815:Epidermal Growth Factor