CORNEAL HEALING PROMOTION WITH FIBRONECTIN PEPTIDES

角膜伤口愈合中的脱落是一个主要的医疗保健问题。 有许多临床状况，其中角膜伤口愈合是 受损，例如单纯疱疹性角膜炎、糖尿病和 风湿性疾病。 角膜愈合也是一个重要的并发症 在涉及角膜和角膜的各种外科手术中， 通过角膜或角膜缘伤口的过度上皮迁移可 使眼前房上皮化， 青光眼 屈光手术的证据表明角膜瘢痕 可能是不可预测和不完整的。 本提案将审查 纤连蛋白片段和化学合成肽的能力， 促进离体和体内角膜上皮创伤模型的愈合 系统. 纤连蛋白是一种多结构域分子，其参与了 眼睛的正常伤口愈合。 外源性FN将促进愈合 慢性角膜溃疡 我们将分离出特定的蛋白水解片段 添加到体外模型中，以确定愈合率是否 增加 接下来的研究将确定这些碎片的影响 或肽在体外促进分离的上皮细胞运动中的作用。 到 在体内研究中，我们接下来将使用放射性标记的FN肽或 片段，并在3种载体中测定体外与角膜的结合， 增加角膜中的肽暴露：聚乙烯醇，凡士林， 和透明质酸。 nexty研究将利用生物活性肽， 载体中的纤连蛋白片段在体内模型系统中的完整和 部分皮层的伤口 将通过评估来监测愈合率 动物角膜连续愈合超过72小时。 组织学样品 并进行形态测定分析，以确认体内 结果 这些研究将有望提供一种有效、安全（避免 血液制品的风险）的方法，该方法使用化学合成的肽， 提供药物，这将促进角膜伤口愈合。 这 也可以应用于眼部疾病， 伤口愈合 这项研究计划的适度成功可能会产生重大影响 严重的医疗保健问题。

Abnormalities in corneal wound healing are a major health care problem. There are a number of clinical conditions where corneal wound healing is compromised, for example, herpes simplex keratitos, diabetes mellitus, and rheumatoid disease. Cornea healing is also an important complicating factor in various surgical procedures involving the cornea and cateracts. Excessive epithelial migration through a corneal or limbal wound can epithelialize the anterior chamber of the eye and cause secondary glaucoma. Evidence from refractive surgery suggests that corneal scarring can be unpredictable and incomplete. This proposal will examine the ability of fibronectin fragments and chemically synthesized peptides to promote in vitro and in vivo corneal epithelial wound healing in model systems. Fibronectin is a multidomain molecule which is involved in the normal wound healing in the eye. Exogenous FN will promote healing of chronic corneal ulcers. We will isolate specific proteolytic fragments added to an in vitro model to determine whether the rate of healing is increased. The next studies will determine the effects of these fragments or peptides in promoting isolated epithelial cell movement in vitro. To aid in vivo studies, we will next use radiolabelled FN peptides or fragments and determine binding to corneas in vitro in 3 vehicles which may increase peptide exposure in the cornea: polyvinyl alcohol, petrolatum, and hyaluronic acid. The nexty studies will utilize bioactive peptides and fragments of fibronectin in vehicles in in vivo model systems of full and partial thickness wounds. Healing rate will be monitored by evaluating corneal healing serially in animals over 72 hours. Histological samples and morphometric analyses will be performed to confirm the in vivo results. The studies will hopefully provide an effective, safe (avoiding the risk of blood products) method using chemically synthesized peptides to deliver pharmaceuticals which will enhance corneal wound healing. This would also have application for diseases of the eye where there is abnormal wound healing. Modest success in this research program could have a major impact on serious health care problems.