PHARMACOLOGY OF AQUEOUS OUTFLOW IN THE HUMAN EYE

描述(改编自申请人的摘要)： 建议的研究是为了获得更多的生理学和 人眼房水流出的药理学。中的一个主要重点 拟议的研究是为了确定cAMP在调节变化中的作用 在流出设施中，总体假设可能有 不止一个环化酶参与调节细胞的反应性 外流系统对肾上腺素、前列腺素等多种刺激， M受体激动剂和Na/K/2Cl共转运调节剂。这个 具体目标包括：(1)鉴定腺苷酸异构体 人流出液组织中环化酶的表达及其药理学特征 CAMP介导的人体流出组织流出；(2)药理学 毒扁豆碱类药物对流出设施增加效应的表征 它直接发生在体外人类流出组织上，并且是 与睫状肌无关，并绘制了 流出通道中的M受体；以及(3)药理作用 类内皮样蛋白亚型的鉴定与鉴定 最近在《流出》中描述的Na/K/2Cl共输送系统 组织。拟议的研究将利用生理、生化 和分子生物学方法提供了更完整的 了解人眼房水流出的调节。 增强对正常流出的基本机制的理解 可能有助于了解原发性开角型青光眼的发病机制 促进改进治疗方法的开发。

DESCRIPTION (Adapted from applicant's abstract): The overall goal of the proposed research is to gain further knowledge of the physiology and pharmacology of aqueous outflow in the human eye. A major emphasis in the proposed studies is to characterize the role of cAMP in mediating changes in outflow facility, with an overall hypothesis that there is probably more than one cyclase involved in mediating the responsiveness of the outflow system to such diverse stimuli as epinephrine, prostaglandins, muscarinic agonists and modulators of Na/K/2Cl co-transport. The specific aims include: (1) identification of isoforms of adenylate cyclase in human outflow tissue and pharmacological characterization of cAMP-mediated outflow in human outflow tissue; (2) pharmacological characterization of the outflow facility increasing-effect of muscarinics which occurs directly on human outflow tissue in vitro and is independent of the ciliary muscle, and mapping of the subtypes of muscarinic receptors in the outflow pathways; and (3) pharmacological characterization and identification of isoforms of the endothelial-like Na/K/2Cl co-transport system which has recently been described in outflow tissue. The proposed studies will make use of physiological, biochemical and molecular biological methods in providing a more complete understanding of the regulation of aqueous outflow in the human eye. Enhanced understanding of the basic mechanisms underlying normal outflow may lend insight into the pathogenesis of primary open angle glaucoma and facilitate development of improved treatments.