B. Raphael et al., ENHANCED HEALING OF CAT CORNEAL ENDOTHELIAL WOUNDS BY EPIDERMAL GROWTH-FACTOR, Investigative ophthalmology & visual science, 34(7), 1993, pp. 2305-2312
Purpose. The authors investigated whether healing of cat corneal endot
helial wounds could be enhanced in vivo by human epidermal growth fact
or (EGF). Methods. EGF was administered in sodium hyaluronate to the a
nterior chamber of cats after an endothelial touch injury. Control con
tralateral eyes received sodium hyaluronate alone. At selected times a
fter injury, the corneas were evaluated for thickness, the rate of end
othelial wound closure, the endothelial cell density, any variation in
cell size, the percentage of hexagonal cells, and endothelial cell mi
tosis. Results. Two days after injury, endothelial wounds of eyes trea
ted with EGF had healed an average of 65 +/- 4% of the initial 38.5 mm
2 wound area; paired control eves 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 mum and 786 versus 728 mum, respectivel
y) 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 mum). Seven d
ays after injury, the corneas treated with EGF had an average of 76 +/
- 28% more (P < 0.05) endothelial cell nuclei labeled with tritiated t
hymidine compared with that of the paired control eyes (2472 versus 15
43 labeled nuclei). Fourteen days after injury, the central endothelia
l cell density of EGF-treated corneas was an average of 38 +/- 11% hig
her than that of the paired control eyes (P < 0.01, 1708 versus 1235 c
ells/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 s
ize for EGF-treated corneas was an average of 31% (P < 0.05) smaller t
han that of the paired control corneas (0.21 versus 0.29 [standard dev
iation]/mean cell size). Conclusions. A single intraocular application
of EGF formulated in sodium hyaluronate after an endothelial cell inj
ury significantly enhanced multiple parameters that are closely relate
d to improved endothelial cell regeneration.