CORNEAL HEALING PROMOTION WITH FIBRONECTIN PEPTIDES

角膜伤口愈合的异常是一个主要的卫生保健问题。 在许多临床情况下，角膜伤口愈合 例如，单纯疱疹病毒性角膜炎、糖尿病和 类风湿病。角膜愈合也是一个重要的并发症。 包括角膜和角膜在内的各种外科手术中的因素。 过多的上皮细胞通过角膜或角膜缘伤口迁移可能 使眼睛前房上皮化，导致继发性 青光眼。屈光手术的证据表明，角膜疤痕 可能是不可预测和不完整的。这项提案将审查 纤维连接蛋白片段和化学合成肽的结合能力 体外和体内促进角膜上皮损伤愈合的实验研究 系统。纤维连接蛋白是一种多结构域分子，它参与了 眼部伤口愈合正常。外源性纤维连接蛋白将促进创面愈合 慢性角膜溃疡。我们将分离特定的蛋白质分解片段 添加到体外模型中以确定治愈率是否 增加了。接下来的研究将确定这些碎片的影响 或促进体外分离的上皮细胞运动的多肽。至 为了帮助活体研究，我们接下来将使用放射性标记的FN多肽或 在3种载体上测定与角膜的结合，这可能 增加角膜中的多肽暴露：聚乙烯醇，凡士林， 和透明质酸。未来的研究将利用生物活性多肽和 FULL和FULL体内模型系统中纤维连接蛋白在车辆中的片段 部分厚伤。治愈率将通过评估 动物的角膜连续愈合超过72小时。组织学标本 并将进行形态测量分析以确认体内的 结果。这些研究有望提供一种有效、安全(避免 血液制品的风险)方法使用化学合成的多肽 提供可促进角膜伤口愈合的药物。这 也适用于有异常情况的眼部疾病 伤口愈合。在这项研究计划中的小成功可能会有一个重大的 对严重的医疗保健问题的影响。

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.