MULLER'S CELL CONTRACTION IN PROLIFERATIVE RETINOPATHIES

与增殖性视网膜病变相关的细胞收缩可能 最终导致视网膜折叠和脱离。这些变化可以是 手术逆转，但复发率高。在某些情况下 这最终会导致失明。细胞收缩会 最终用分子术语描述和控制 治疗剂。使用细胞收缩的体外实验 建议重点研究穆勒细胞的收缩活动，其 增殖性玻璃体视网膜病变的相关因素 更早的研究。该提案的第一阶段概述了一项关于 已知的生物活性多肽对穆勒细胞的影响 收缩将是确定的。这将使我们能够识别 血清中的活性物质，由内皮细胞和视网膜分泌 色素上皮细胞被认为各自参与了 增殖性疾病。这也将使我们能够确定 在这些相关来源中存在未知生物活性多肽。这个 这些研究的相关性最终将在一项关于 正常人和病理性人的促收缩潜能 玻璃体。我们将最终确定两者之间的相关性 生物活性多肽的水平和种类与疾病状态。二 对穆勒细胞收缩的机制研究将确定 参与传递收缩信号的细胞质第二信使 并确定参与传播细胞表面受体的 由细胞骨架产生的收缩力。这三项研究 可能产生的信息将使三种方法能够防止 1)靶向中和细胞介导的视网膜脱离 促收缩因子，2)抑制细胞质第二 信使，以及3)阻断参与传播的整合素受体 收缩力。

Cellular contraction associated with proliferative retinopathies can ultimately cause retinal folding and detachment. These changes can be reversed by surgery, but the rate of recurrence is high. In some cases this ultimately causes loss of vision. Cellular contraction will ultimately be described in molecular terms and controlled with therapeutic agents. Using an in vitro assay of cellular contraction we propose to focus on the contractile activities of Muller's cells, whose involvement in proliferative vitreoretinopathy is strongly implied by earlier studies. The first phase of this proposal outlines a study in which the effects of known bioactive peptides on Muller's cell contraction will be determined. This will enable us to identify the active species in serum, secreted by endothelial cells and retinal pigment epithelial cells which are each thought to be involved in proliferative disorders. This will also enable us to determine the existence of unknown bioactive peptides in these relevant sources. The relevance of these studies will ultimately be confirmed in a survey of the contraction-promoting potential of normal and pathologic human vitreous. We will ultimately determine the correlation between the levels and species of bioactive peptides with disease state. Two mechanistic studies of Muller's cell contraction will identify the cytoplasmic second messenger involved in propagating contractile signals and identify the cell surface receptors involved in propagating the contractile forces generated by the cytoskeleton. These three studies could yield information which would enable three approaches to preventing cell-mediated retinal detachment by 1) neutralizing targeted contraction-promoting factors, 2) inhibiting cytoplasmic second messengers, and 3) blocking integrin receptors involved in propagating contractile force.