CORNEAL WOUND HEALING AND OPIOID GROWTH FACTOR

角膜上皮是角膜的主要保护屏障， 创伤或手术后角膜上皮的完全恢复 是恢复正常视觉功能的关键 的 负责维护和修理的机制和因素 角膜上皮不清楚。 我们发现， 阿片样物质系统（EOS）调节兔角膜上皮外植体生长， 培养和体内的上皮再形成以及体内平衡。 此外，委员会认为， 阿片样生长因子（OGF），[Met/5]-脑啡肽，及其受体， zeta存在于角膜的基底细胞和基底上细胞中 人类和动物的上皮。 OGF是一种天然的，具有紧张活性的， 抑制性生长因子，其靶向于生长相关事件。 使用阿片样物质拮抗剂如纳洛酮（NTX）阻断OGF作用， 显著刺激角膜上皮细胞的增殖和迁移， 外植体中的上皮细胞，器官培养中的再上皮化， 体内，以及上皮细胞和角膜缘细胞的DNA合成。 这笔赠款 探讨了EOS在维持和 恢复角膜上皮。 具体目标包括：（1）定义 OGF的存在和位置，OGF激素（前脑啡肽原）的mRNA， zeta受体和上皮、利姆布斯中的OGF结合位点，以及 正常角膜结膜。(2)检查存在、响应和 EOS在兔角膜损伤修复过程中的作用 EOS与细胞增殖、迁移和凋亡的关系 分化，再上皮化和愈合， 确立了习 使用过量OGF和阻断OGF受体的范例 交互作用将被用来理解EOS功能。(3)阐明 嗜酸性粒细胞对兔角膜稳态影响(4)研究的影响 人角膜上皮中EOS对细胞增殖、迁移和 分化，以及细胞/组织组织，利用外植体。 (5)确定EOS在人角膜上皮、利姆布斯中的生物学特性， 在维持、损伤和再上皮化过程中， 器官培养模式 这些研究是一项长期计划的一部分 旨在了解角膜炎的发病机制和治疗 疾病，特别是角膜上皮的病症。

The corneal epithelium is the main protective barrier for the cornea, and complete restoration of the corneal epithelium following trauma or surgery is essential for the restitution of normal visual function. The mechanism(s) and factors responsible for the maintenance and repair of the corneal epithelium are unclear. We have discovered that an endogenous opioid system (EOS) modulates rabbit corneal epithelial explant outgrowth, re-epithelialization in culture and in vivo, and homeostasis. Moreover, both the opioid growth factor (OGF), [Met/5]-enkephalin, and its receptor, zeta, are present in the basal and suprabasal cells of the corneal epithelium of humans and animals. OGF is a native, tonically active, inhibitory growth factor that is targeted to growth-related events. Blockage of OGF action using opioid antagonists such as naltrexone (NTX), dramatically stimulates the proliferation and migration of corneal epithelial cells in explants, re-epithelialization in organ culture and in vivo, and DNA synthesis of epithelial and limbal cells. This grant explores the hypothesis that an EOS plays a role in the maintenance and restitution of the corneal epithelium. Specific aims include: (1) Define the presence and location of OGF, mRNA for OGF hormone (preproenkephalin), zeta receptor, and OGF binding sites in the epithelium, limbus, and conjunctiva of normal cornea. (2) Examine the presence, response, and function of the EOS in rabbit cornea in vivo during injury and repair. The relationship of EOS to cell proliferation, migration, and differentiation, and re-epithelialization and healing, will be established. Paradigms using excess OGF and blockade of OGF-receptor interaction will be employed to understand EOS function. (3) Elucidate the influence of EOS on homeostasis of rabbit cornea. (4) Study the influence of EOS in human corneal epithelium on cell proliferation, migration, and differentiation, as well as cell/tissue organization, utilizing explants. (5) Ascertain the biology of EOS in human corneal epithelium, limbus, and conjunctiva during maintenance, injury, and re-epithelialization using an organ culture model. These studies are part of a long-range program directed towards understanding the pathogenesis and treatment of corneal diseases, particularly disorders of the corneal epithelium.