Reepithelialization of the human cornea is regulated by endogenous opioids

PURPOSE. TO determine the influence of endogenous opioid modulation on reep ithelialization of the human cornea. METHODS. Eight-millimeter-diameter epithelial defects were created with a t rephine and mechanical scraping in the center of human corneas. Resurfacing was studied in organ culture. The size of the defect, the number of specim ens with complete reepithelialization, and rate of closure were evaluated u sing topical fluorescein and morphometric analysis. The influence of opioid receptor blockade was studied using the potent and long-acting opioid anta gonist, naltrexone (NTX; 10(-6) IM), and the effects of excess (10(-6) IM) opioid growth factor (OGF), [Met(5)]enkephalin, also were determined. The m odulatory activity of NTX and OGF on DNA synthesis was evaluated by monitor ing the labeling index (LI) using radioactive thymidine. The presence and l ocation of OGF and its receptor (OGFr) were ascertained by immunocytochemis try 1 hour and 24 hours after abrasion. RESULTS. NTX accelerated the wound-healing process, with 21% to 89% less de fect than controls observed from 24 to 96 hours. At 72 hours, 62% of the su bjects in the NTX group had complete closure of the corneal defects, in con trast to only 19% of the control specimens. All epithelial abrasions were r esurfaced in the NTX group between 96 and 120 hours, whereas all controls w ere not closed until 168 hours. The rate of healing in the NTX group was 1. 06 mm(2)/h compared to a rate of 0.68 mm(2)/h in the control group. OGF del ayed corneal wound healing, with 24% to 260% more defect recorded than in c ontrol specimens at day 7. The healing rate of the OGF group was 0.42 mm(2) /h compared to 0.82 mm(2)/h for control subjects. The corneal epithelium ad jacent to the wound had an LI that was 152% greater than control specimens, whereas OGF decreased the ii of this region by 75%. OGF and OGFr were dete cted in the epithelium bordering the damaged region at 1 hour, and both pep tide and receptor were noted in the regenerating epithelium at 24 hours. CONCLUSIONS. These results indicate that an endogenous opioid is present an d functions as a tonically active, receptor-mediated, negative growth facto r during reepithelialization of the abraded human cornea.