Opioid growth factor regulates dna synthesis in the mammalian ocular surface

An endogenous opioid system (EOS), comprised of the opiotd growth factor (OGF), [Met⁵]-enkephalin, and the zeta (f) opioid receptor, modulates cell proliferation, migration, and organization, and healing of the mammalian corneal epithelium. The present study inquires whether homeostasis of the corneal (CE), limbal (LS), and conjunctival (CA) epithelia in rats is governed by OGF. Initial studies using autoradiography showed no circadian rhythm of DNA synthesis in the CE, LS, or CA. Opioid-receptor blockade by systemic injection of the opioid antagonist, naltrexone (NTX), increased the labeling index (LI) of the CE, LS, and CA by 72.3%, 30.0% and 34.9%, respectively, from control (CO) levels. Injection of OGF (10 mg/kg) decreased the LI in the CE, LS, and CA by 24.8%, 48.2%, and 49.6%, respectively, from CO values. The effects of OGF were found to be receptor mediated because naloxone (10 mg/kg) blocked OGF action. Organ culture studies of the eye showed that NTX increased the LI of the CE, LS, and CA by 106%, 23.6%, and 58.9%, respectively, from CO levels. These results indicate that an EOS tonically and directly inhibits DNA synthesis in ocular surface epithelium, and does so in a receptor mediated fashion. The data lead us to suggest that opioid-receptor interaction is integral to homeostatic maintenance of cellular renewal in the cornea.