CORNEAL WOUND HEALING AND OPIOID GROWTH FACTOR

角膜上皮是保护角膜的主要屏障， 外伤或手术后角膜上皮的完全恢复 对于恢复正常的视觉功能是必不可少的。这个 维护和维修的机制(S)和负责因素 角膜上皮细胞尚不清楚。我们发现一种内源性的 阿片系统(EOS)调控兔角膜上皮细胞生长 在培养和体内重新上皮化，以及动态平衡。此外， 阿片生长因子(OGF)，[Met/5]-脑啡肽及其受体， Zeta存在于角膜的基底层和基底层以上的细胞中。 人和动物的上皮组织。OGF是一种原生的，音质活跃的， 针对生长相关事件的抑制生长因子。 使用阿片类拮抗剂如纳曲酮(NTX)阻断OGF的作用， 极大地刺激角膜的增殖和迁移 外植体中的上皮细胞，器官培养中的再上皮化 活体，以及上皮细胞和角膜缘细胞的DNA合成。这笔赠款 探索EOS在维护和维护过程中起作用的假设 角膜上皮的修复。具体目标包括：(1)明确 OGF、OGF激素(前脑啡肽原)mRNA的存在和定位， Zeta受体和OGF结合部位位于上皮、角膜缘和 正常角膜的结膜。(2)检查存在、响应和 EOS在活体兔角膜损伤修复过程中的作用 嗜酸性粒细胞与细胞增殖、迁移和 分化，重新上皮化和愈合，将是 已经成立了。过度使用OGF和阻断OGF受体的范式 将利用交互作用来理解状态方程的功能。(3)澄清 EOS对兔角膜动态平衡的影响。(四)研究影响 人角膜上皮细胞中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)确定人角膜上皮、角膜缘和角膜缘中EOS的生物学特性。 结膜在维持、损伤和再上皮化过程中使用 器官培养模型。这些研究是一个长期计划的一部分。 旨在了解角膜的发病机制和治疗方法 疾病，特别是角膜上皮的紊乱。

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.