Zagon I S, Sassani J W, Kane E R, McLaughlin P J
Department of Neuroscience and Anatomy, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA.
Brain Res. 1997 Jun 6;759(1):92-102. doi: 10.1016/s0006-8993(97)00238-2.
Endogenous opioid peptides serve as growth factors in developing, renewing, and neoplastic cells and tissues. This study examined the hypothesis that opioids serve to modulate the homeostatic renewal of ocular surface epithelium in the rat. DNA synthesis in the epithelium of the central (CC) and peripheral (PC) cornea, limbus (LM), and conjunctiva (CN) was investigated using adult male rats. Animals received an injection of opioid growth factor (OGF), [Met5]-enkephalin, OGF and naloxone (NAL), NAL alone, naltrexone (NTX), or an equivalent volume of sterile water (CO) and sacrificed 4 h later (i.e. 16:00 h). [3H]thymidine was administered 1 h before sacrifice. With the exception of NTX (20 mg/kg), all compounds were given at 10 mg/kg. Examination of 5 time points over an 18-h period revealed no variation in DNA synthesis within a region of ocular surface basal epithelium (BE). OGF depressed DNA synthesis of the BE by 25, 48, and 50% in the PC, LM, and CN, respectively; little labeling was recorded in the BE of the CC. Exposure to OGF-NAL or NAL alone did not alter DNA synthesis of the BE. Complete blockade of OGF-zeta receptor interaction by administration of the potent opioid antagonist, NTX, increased the number of epithelial cells in the PC, LM, and CN undergoing DNA synthesis by 30 to 72%. The effects of OGF and NTX on DNA synthesis of BE also were observed in an organ culture setting. Utilizing immunocytochemistry, OGF and its receptor zeta were associated with both the basal and the suprabasal cells of the ocular surface epithelium. These results indicate that an endogenous opioid peptide, OGF, and its receptor are present and govern homeostatic cellular renewal processes in ocular surface epithelium. OGF regulates DNA synthesis in a direct manner, and does so by a tonic, inhibitory, and receptor-mediated mechanism.
内源性阿片肽在发育、更新及肿瘤性细胞和组织中发挥生长因子的作用。本研究检验了阿片类物质可调节大鼠眼表上皮稳态更新的假说。使用成年雄性大鼠研究中央角膜（CC）、周边角膜（PC）、角膜缘（LM）和结膜（CN）上皮中的DNA合成。动物接受阿片生长因子（OGF）、[Met5] - 脑啡肽、OGF和纳洛酮（NAL）、单独的NAL、纳曲酮（NTX）或等量无菌水（CO）注射，并于4小时后（即16:00时）处死。在处死前1小时给予[3H]胸腺嘧啶核苷。除NTX（20 mg/kg）外，所有化合物均以10 mg/kg给药。在18小时期间对5个时间点的检查显示，眼表基底上皮（BE）区域内的DNA合成没有变化。OGF分别使PC、LM和CN中BE的DNA合成降低25%、48%和50%；CC的BE中几乎没有标记记录。暴露于OGF - NAL或单独的NAL并未改变BE的DNA合成。通过给予强效阿片拮抗剂NTX完全阻断OGF - ζ受体相互作用，使PC、LM和CN中进行DNA合成的上皮细胞数量增加30%至72%。在器官培养环境中也观察到了OGF和NTX对BE DNA合成的影响。利用免疫细胞化学方法，发现OGF及其受体ζ与眼表上皮的基底细胞和基底上层细胞均有关联。这些结果表明，一种内源性阿片肽OGF及其受体存在于眼表上皮中，并调控其稳态细胞更新过程。OGF以直接方式调节DNA合成，且通过一种持续性、抑制性和受体介导的机制来实现。
