PATHOGENSIS OF RETINAL ISCHEMIC INJURY

增生性玻璃体视网膜病变（PVR）的特征是异常的 视网膜和玻璃体两个表面上的细胞增殖 面，胶原蛋白和其他细胞外基质材料的沉积，以及 最终形成的膜收缩，导致视网膜牵引 支队 视网膜病变是视网膜病变最常见的原因。 视网膜复位手术失败。 刺激细胞的因素 尽管纤维连接蛋白和血小板衍生物 生长因子最近也受到牵连。 建议的目的 研究是为了更好地了解疾病，通过确定机制， 导致细胞增殖和膜收缩， 发展预防手段。 我们假设花生四烯酸代谢的改变和 视网膜脱离手术后血眼屏障的破坏 或其它创伤导致物质在玻璃体中积聚 腔，刺激趋化性，附着，收缩， 细胞在可用的或新合成的细胞外基质上增殖 矩阵 我们建议通过干扰 花生四烯酸代谢、细胞附着和细胞收缩 以确定我们是否可以阻止细胞增殖和收缩， 用于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抑制剂阻断， 环氧合酶和脂氧合酶途径以及这两种途径的抑制剂 途径。 将在动物中确定对细胞增殖的影响 增生性玻璃体视网膜病变模型。 延时摄影和 计算机图像分析将用于评估牵引力 通过培养的细胞施加在硅橡胶基质上。 粘附 蛋白质将被去除，平滑肌收缩的抑制剂将 为了确定对细胞收缩的影响， 体外和体内增殖。 最后，药物组合将 评价疗效，并将使用动物进行类似的实验 眼睛（猫，灵长类动物）对伤害的反应更类似于 比兔子更像人类。 这些研究的结果将有助于更好地了解 眼内细胞异常增殖的机制， 导致预防或影响PVR早期进程的方法， 其他眼部增生性疾病。

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.