Re-epithelialization of the rabbit cornea is regulated by opioid growth factor

An endogenous opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF) is a tonically active, autocrine-produced inhibitory molecule related to developing, neoplastic, renewing and healing tissues. The present investigation was designed to examine the role of OGF on corneal epithelial wound closure in the rabbit under in vitro and in vivo conditions. A 10-mm diameter epithelial defect was made in the center of the rabbit cornea, and the size of the defect, number of specimens with complete re-epithelialization, and rate of wound closure were evaluated using topical fluorescein and morphometric analysis. In organ culture, the influence of a complete opioid receptor blockade by naltrexone (NTX) showed an acceleration in re-epithelialization compared to controls. The action of excessive agonist (OGF) application revealed that exposure of wounded epithelium to OGF delayed wound closure under in vitro conditions, and did so in a receptor-mediated fashion. The modulatory capability of opioids on wound healing in vivo was explored by examining the effects of opioid peptide-receptor disruption using topical application of NTX, and enhanced healing of the abraded rabbit cornea was noted. The presence and location of OGF and the zeta (zeta) receptor in the normal and injured rabbit corneal epithelium were ascertained by immunocytochemistry, and both OGF and the zeta receptor were detected in basal and suprabasal epithelial cells. These results show that an opioid peptide, OGF, plays a direct role in the repair of injury to the corneal epithelium in the rabbit and acts as a receptor-mediated and constitutively expressed inhibitory molecule.