Opioid dependent modulation of ocular surface epithelial DNA synthesis

Purpose. To determine the role of the endogenous opioid system (EOS) in the modulation of ocular surface epithelial DNA synthesis in the rat eye. Methods. Three hrs after the systemic injection of 10 mg/kg opioid growth factor, ([Met⁵]-enkephalin, OGF), naloxone (NAL), or naltrexone (NTX), [³H] thymidine (10 μCi/g body weight) was injected ip. in adult Sprague-Dawley rats. Four hrs after injection of OGF, NAL, or NTX, animals were euthanized, and the ocular anterior segments histologically sectioned and processed for autoradiography. Similar studies utilizing NTX were performed on organ cultured whole eyes. Results. The labeling index (LI) of corneal (CE), limbal (LE), and conjunctival (CJ) epithelium was increased 72.3%, 30.0%, and 34.9%, respectively, relative to control values (CO) in response to the opioid antagonist, NTX, in living rats. In organ cultured whole eyes, the LI was increased by 106%, 23.6%, and 58.9% in CE, LE, and CJ, respectively. The LI was decreased by 24.8%, 48.2%, and 49.6% in CE, LE, and CJ, respectively, relative to CO in response to OGF in living rats. The effect of OGF was blocked by concurrent treatment with the receptor specific opioid antagonist, NAL. NAL alone had no effect on DNA synthesis. Conclusion. Ocular surface epithelial DNA synthesis is tonically modulated by an EOS in a receptor dependent manner.