PATHOGENSIS OF RETINAL ISCHEMIC INJURY

增殖性玻璃体视网膜病变(PVR)的特征是异常 视网膜和玻璃体表面细胞的增殖 面部、胶原和其他细胞外基质材料的沉积，以及 最终形成的膜收缩，导致视网膜牵拉 超然。增殖性玻璃体视网膜病变是最常见的原因 视网膜复位术失败。刺激细胞的因素 目前尚不清楚生长情况，尽管纤维连接蛋白和血小板来源于 生长因子最近被认为与此有关。建议的目的是 研究旨在通过确定发病机制来更好地了解这种疾病。 导致细胞增殖和膜收缩，从而 发展预防手段。 我们假设花生四烯酸代谢的变化和 视网膜脱离手术后血眼屏障的破坏 或其他创伤导致玻璃体内物质积聚 刺激趋化性、依附、收缩和 细胞在可用的或新合成的胞外上的增殖 矩阵。我们建议通过干扰来检验这一假设 花生四烯酸代谢、细胞附着和细胞收缩的顺序 为了确定我们是否可以阻止细胞的增殖和收缩 增殖性玻璃体视网膜病变的体外和动物模型。 花生四烯酸代谢将被选择性的 环氧合酶和脂氧合酶途径及其抑制物 小路。对细胞增殖的影响将在动物身上确定。 增殖性玻璃体视网膜病变模型。延时摄影和 将使用计算机图像分析来评估牵引力 培养细胞施加在硅橡胶衬底上。粘附性 蛋白质将被去除，平滑肌收缩的抑制剂将 以确定对细胞收缩的影响和 体外和体内增殖。最后，药物的组合将是 疗效评估和类似的实验将在动物身上进行 眼睛(猫、灵长类)对伤害的反应更类似于 人比兔子强。 这些研究的结果将有助于更好地了解 参与眼睛细胞异常增殖的机制，并可能 导致预防或影响PVR早期病程的手段 眼部其他增生性疾病。

Proliferative vitreoretinopathy (PVR) is characterized by abnormal proliferation of cells on both surfaces of the retina and the vitreous face, deposition of collagen and other extracellular matrix materials, and eventual contraction of the membranes formed, resulting in traction retinal detachment. Proliferative vitreoretinopathy is the most common cause of failure in retinal reattachment surgery. The factors that stimulate cell growth are at present unknown although fibronectin and platelet derived growth factor have recently been implicated. The purposes of the proposed studies are to better understand the disease by determining the mechanisms that lead to the cellular proliferation and membrane contraction and to develop means of prevention. We hypothesize that alterations in arachidonic acid metabolism and breakdown of the blood ocular barriers following retinal detachment surgery or other trauma results in the accumulation of substances in the vitreous cavity that stimulate chemotaxis, attachment, contraction, and proliferation of cells on available or newly synthesized extracellular matrices. We propose to test this hypothesis by interfering with arachidonic acid metabolism, cell attachment, and cell contraction in order to determine if we can prevent cellular proliferation and contraction in vitro and in animal models for proliferative vitreoretinopathy. Arachidonic metabolism will be blocked by selective inhibitors of the cyclo-oxygenase and lipoxygenase pathways as well as by inhibitors of both pathways. The effect on cell proliferation will be determined in animal models of proliferative vitreoretinopathy. Time lapse photography and computerized image analysis will be used to evaluate tractional forces exerted on a silicone rubber substratum by cultured cells. Adhesion proteins will be removed and inhibitors of smooth muscle contraction will be applied in order to determine the effect on cell contraction and proliferation in vitro and in vivo. Finally, combinations of drugs will be evaluated for efficacy and similar experiments will be done using animal eyes (cat, primate) that have a response to injury that is more similar to human than is rabbit. The results of these studies will lead to a better understanding of the mechanisms involved in abnormal proliferation of cells in the eye and could lead to means of preventing or influencing the early course of PVR and other proliferative diseases of the eye.