CONTROL OF CORNEAL HYDRATION AND TRANSPARENCY

本提案的目标是了解控制 液体流入和流出角膜透明性是 通常是由于浮肿，在基质中过度积聚液体 这会导致它膨胀并变得不透明。太阳光下的一层电池 后表面，即内皮，控制着血管的水合。 通过允许从基质中引入有限数量的液体 房水(渗漏)，并通过能量排出等量的- 独立的主动输送过程(泵)。拟议的目标将 检查泵和泄漏功能的三种机制 血管内皮细胞可能受到调控。每项研究都包括 将采用生化、药理学和生理学方法 使用完整的角膜，使观察结果与 基质的水合状态。目标1研究转导通路 (第二信使)和效应机制(钠泵、离子 渠道，渗透性)，中介改善(即，减少)水合作用 对腺苷的反应。目标2研究信令问题 (反馈)来自间质水合或内皮细胞体积 在泵或泄漏功能的调整中。《目标3》考察了 内皮细胞结构(紧密连接、细胞骨架)的依赖性 和酶活性(Na+-K+-ATPase、Cyclase、Kinase)对内源的影响 三磷酸腺苷水平。了解这些调节流体的系统 内皮细胞的运输特性为 刺激泵活动或减少的治疗性干预 泄漏，从而控制在以下情况下出现的浮肿 糖尿病或肝炎角膜炎。

The goal of this proposal is to understand the processes that control the movements of the fluid into and out of the corneal transparency is frequently due to edema, an exessive accumulation of fluid in the stroma which causes it to swell and become opaque. The sungle layer of cells on the posterioe surface, the endothelium, controls the hydration of the stroma by allowing a limited amount of fluid to be drawn in from the aqueous humor (the leak), and expelling an equivalent amount by energy- dependent active transport process (the pump). The proposed Aims will examine three mechanisms by which the pump and leak function of the endothelial cells may be regulated. Each of the studies, which encompass biochemical, pharmacological and physiological approaches, will be done with whole corneas, allowing direct correlation of the observations with the hydration state of stroma. Aim 1 examines the transduction pathways (second messengers) and the effector mechanisms (sodium pump, ion channels, permeability) that mediate improves (i.e., decreased) hydration in response to adenosine. Aim 2 studies the question of of signalling (feedback) from stromal hydration or volume of the endothelial cells themselves in regualtion of pump or leak funcations. Aim 3 examines the dependence of endothelial cell structure (tight junctions, cytoskeleton) and enzyme activity (Na+-K+ATPase, cyclase, kinase) on the endogenous levels of ATP. Understanding these systems that modulate the fluid transport characteristics of the endothelium create opportunity for therapeutic intervention that would stimulate pump activity or decrease the leak, thereby controlling the edema seen in such conditions as diabetes or hepetic keratitis.