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Ian S. Zagon, Joseph W. Sassani, Patricia J. McLaughlin; Reepithelialization of the Human Cornea Is Regulated by Endogenous Opioids. Invest. Ophthalmol. Vis. Sci. 2000;41(1):73-81.
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purpose. To determine the influence of endogenous opioid modulation on
reepithelialization of the human cornea.
methods. Eight-millimeter-diameter epithelial defects were created with a
trephine and mechanical scraping in the center of human corneas.
Resurfacing was studied in organ culture. The size of the defect, the
number of specimens with complete reepithelialization, and rate of
closure were evaluated using topical fluorescein and morphometric
analysis. The influence of opioid receptor blockade was studied using
the potent and long-acting opioid antagonist, naltrexone (NTX;
10−6 M), and the effects of excess (10−6 M)
opioid growth factor (OGF), [Met5]enkephalin, also were
determined. The modulatory activity of NTX and OGF on DNA synthesis was
evaluated by monitoring the labeling index (LI) using radioactive
thymidine. The presence and location of OGF and its receptor (OGFr)
were ascertained by immunocytochemistry 1 hour and 24 hours after
results. NTX accelerated the wound-healing process, with 21% to 89% less
defect than controls observed from 24 to 96 hours. At 72 hours, 62% of
the subjects in the NTX group had complete closure of the corneal
defects, in contrast to only 19% of the control specimens. All
epithelial abrasions were resurfaced in the NTX group between 96 and
120 hours, whereas all controls were not closed until 168 hours. The
rate of healing in the NTX group was 1.06 mm2/h compared to
a rate of 0.68 mm2/h in the control group. OGF delayed
corneal wound healing, with 24% to 260% more defect recorded than in
control specimens at day 7. The healing rate of the OGF group was 0.42
mm2/h compared to 0.82 mm2/h for control
subjects. The corneal epithelium adjacent to the wound had an LI that
was 152% greater than control specimens, whereas OGF decreased the LI
of this region by 75%. OGF and OGFr were detected in the epithelium
bordering the damaged region at 1 hour, and both peptide and receptor
were noted in the regenerating epithelium at 24 hours.
conclusions. These results indicate that an endogenous opioid is present and
functions as a tonically active, receptor-mediated, negative growth
factor during reepithelialization of the abraded human
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