CORNEAL ENDOTHELIAL REPAIR--ROLE OF LIPID MEDIATORS

这个项目的总体目标是阐明这些机制。 管理角膜内皮的伤口修复。中环 在拟议的研究中要探索的假设是花生四烯酸 因损伤或损伤而合成的衍生脂质介体 细胞外信号调节角膜的进程 内皮细胞通过其有丝分裂和分化的周期。这个 拟议研究的目的是： 1)确定角膜内皮的调节脂质介质， 2)通过有丝分裂和有丝分裂来表征这种介质的产生 分化内皮细胞， 3)确定受体依赖的信号转导是否在 有丝分裂和分化的内皮细胞， 4)探索受体后信号效应通路 脂质介质对角膜有丝分裂和分化的调节 血管内皮细胞和 5)比较了脂质介导的有丝分裂和分化的调节 兔角膜内皮细胞。 这些问题将用有丝分裂、分化和 组织内培养兔角膜内皮细胞伤口闭合模型的建立 培养，并采用人角膜内皮器官培养模型。 调节有丝分裂和分化的脂质介质将是 通过细胞化学检测细胞周期和 分化标记。介体的生物合成及其调控 受体介导的事件将使用生化示踪剂来确定， 生物合成酶的免疫测定和第二代的生化测定 信使。细胞内效应通路的参与将是 使用药理探针改变信号转导的研究 小路。 发现可改变兔有丝分裂和分化的脂质介质 角膜内皮细胞也将使用器官培养模型进行测试 和营养不良的人角膜内皮。从以下方面获得的结果： 这些研究将提出强化角膜的治疗策略。 意外或手术创伤后的内皮伤口修复。

The overall objective of this project is to elucidate the mechanisms governing wound repair in the corneal endothelium. The central hypothesis to be explored in the proposed studies, is that arachidonate derived lipid mediators synthesized in response to injury or to extracellular signals modulate the progression of the corneal endothelial cell through its cycle of mitosis and differentiation. The aims of the proposed study are to: 1) identify the modulatory lipid mediators of the corneal endothelium, 2) characterize the production of such mediators by mitotic and differentiating endothelial cells, 3) determine if receptor-dependent signal transduction is regulated in mitotic and differentiated endothelial cells, 4) explore post-receptor signal signal effector pathways that govern lipid mediator regulation of mitosis and differentiation in corneal endothelial cells and 5) compare lipid mediated regulation of mitosis and differentiation in rabbit human corneal endothelial cells. These questions will be investigated using mitotic, differentiated and wound closure models of rabbit corneal endothelial cells grown in tissue culture, and using organ culture models of human corneal endothelium. Lipid mediators regulating mitosis and differentiation will be identified using cyctochemical detection of cell cycle and differentiation markers. Biosynthesis of mediators and regulation of receptor mediated events will be determined using biochemical tracers, immunoassay of biosynthetic enzymes and biochemical assay of second messengers. The involvement of intracellular effector pathways will be investigated using pharmacological probes to alter signal transduction pathways. Lipid mediators found to alter mitosis and differentiation of rabbit corneal endothelium will also be tested using organ culture models of and dystrophic human corneal endothelium. The results obtained from these studies will suggest therapeutic strategies for enhancing corneal endothelial wound repair subsequent to accidental or surgical trauma.