MULLER'S CELL CONTRACTION IN PROLIFERATIVE RETINOPATHIES

与增生性视网膜病变相关的细胞收缩可以 最终导致视网膜折叠和脱离。 这些变化可以 手术可以逆转，但复发率很高。 在一些情况下 这最终导致视力丧失。 细胞收缩将 最终用分子术语来描述， 治疗剂。 使用体外细胞收缩试验， 我建议把重点放在穆勒细胞的收缩活动， 参与增生性玻璃体视网膜病变是强烈暗示， 早期的研究。 该提案的第一阶段概述了一项研究， 已知的生物活性肽对Muller细胞的作用 收缩将被确定。 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，每一个都被认为是参与 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的生物活性肽。 的 这些研究的相关性最终将在一项调查中得到证实， 正常人和病理人促收缩潜力 玻璃的。 我们将最终确定 生物活性肽的水平和种类与疾病状态的关系。 两 Muller细胞收缩的机制研究将确定 参与传播收缩信号的细胞质第二信使 并确定参与繁殖的细胞表面受体， 由细胞骨架产生的收缩力。 这三项研究 可以提供信息，使三种方法能够防止 细胞介导的视网膜脱离，通过1）中和靶向 收缩促进因子，2）抑制细胞质第二 信使，和3）阻断整合素受体参与繁殖 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.