OPIOID GROWTH-FACTOR MODULATES CORNEAL EPITHELIAL OUTGROWTH IN TISSUE-CULTURE

In addition to neuromodulation, endogenous opioid peptides serve as gr owth factors. To determine involvement of opioids in the homeostatic r enewal and repair of the corneal epithelium, epithelial outgrowths fro m 3-mm explants of rabbit cornea were investigated. Blockade of opioid -receptor interaction by the potent opioid antagonist naltrexone (NTX) for 7 days significantly increased the extent of outgrowths and the n umber and labeling index (DNA synthesis) of epithelial cells, relative to control levels. Outgrowths exposed to the opioid growth factor (OG F) [Met(5)]enkephalin for 7 days were subnormal in extent and labeling index and displayed alterations in architectural pattern. The effects of OGF on epithelial outgrowth were blocked by concomitant exposure t o the opioid antagonist naloxone; naloxone alone had no effect on grow th at the concentration utilized. NTX and OGF were active in both seru m-containing and serum-free cultures. Immunocytochemical investigation s showed that both OGF and its opioid receptor zeta (5) were present i n epithelial cells growing in control media. The results indicate that an endogenous opioid peptide and its receptor are present in mammalia n corneal epithelium and serve to modulate cell proliferation, migrati on, and organization.