Enhanced healing of cat corneal endothelial wounds by epidermal growth factor.
OBJECTIVE
The authors investigated whether healing of cat corneal endothelial wounds could be enhanced in vivo by human epidermal growth factor (EGF).


METHODS
EGF was administered in sodium hyaluronate to the anterior chamber of cats after an endothelial touch injury. Control contralateral eyes received sodium hyaluronate alone. At selected times after injury, the corneas were evaluated for thickness, the rate of endothelial wound closure, the endothelial cell density, any variation in cell size, the percentage of hexagonal cells, and endothelial cell mitosis.


RESULTS
Two days after injury, endothelial wounds of eyes treated with EGF had healed an average of 65 +/- 4% of the initial 38.5 mm2 wound area; paired control eyes had healed an average of 59 +/- 4% (P < 0.05). Both EGF-treated and control wounds had resurfaced over 90% of the initial wound area on day 4 after injury, and the wounds were completely resurfaced by 7 and 14 days after injury in both treatment groups. On days 4 and 7 after injury, the EGF-treated corneas were 5% and 8% thicker (835 versus 796 microns and 786 versus 728 microns, respectively) than the paired control corneas (P < 0.03). On days 10 and 14 after injury, both EGF-treated and control corneas were 19% and 12% thicker, respectively, than prewound the corneal thickness (621 microns). Seven days after injury, the corneas treated with EGF had an average of 76 +/- 28% more (P < 0.05) endothelial cell nuclei labeled with tritiated thymidine compared with that of the paired control eyes (2472 versus 1543 labeled nuclei). Fourteen days after injury, the central endothelial cell density of EGF-treated corneas was an average of 38 +/- 11% higher than that of the paired control eyes (P < 0.01, 1708 versus 1235 cells/mm2). The percentage of hexagonal cells in the wound area was an average of 14 +/- 4% higher (P < 0.01) than that of the paired control eyes (82% versus 69%), and the coefficient of variation of the cell size for EGF-treated corneas was an average of 31% (P < 0.05) smaller than that of the paired control corneas (0.21 versus 0.29 [standard deviation]/mean cell size).


CONCLUSIONS
A single intraocular application of EGF formulated in sodium hyaluronate after an endothelial cell injury significantly enhanced multiple parameters that are closely related to improved endothelial cell regeneration.
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky.
B
B
Raphael
N C
NC
Kerr
R W
RW
Shimizu
J H
JH
Lass
K C
KC
Crouthamel
S R
SR
Glaser
G A
GA
Stern
B J
BJ
McLaughlin
D C
DC
Musch
E
E
Duzman
D000818:Animals; D002415:Cats; D002452:Cell Count; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D004261:DNA Replication; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D006820:Hyaluronic Acid