PHYSIOLOGY OF THE CILIARY EPITHELIAL BILAYER OF THE EYE

眼睛双层睫状上皮的生理学

基本信息

批准号：
2019761
负责人：
MARVIN L SEARS
金额：
$ 43.98万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-01-19 至 1998-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (adapted from applicant's abstract): The objective of this proposal is to learn the cellular and molecular characteristics of the transporting systems for aqueous secretion by studying transepithelial transport across the ciliary epithelium of the eye. A completely new sort of membrane preparation of the isolated bilayered ciliary epithelium has been developed to facilitate these studies. Studies of this bilayer would be compared to single layer preparations of the pigmented and non-pigmented epithelium that have also been obtained. The bioelectric characteristics of this preparation, the transepithelial potential difference, resistance and short circuit current would be determined. Electrical and tracer methods would be used to examine the mechanisms for ion permeation. For example, the separate contributions of sodium, chloride and bicarbonate to the net current across these cellular preparations and their interactions would be studied. What fractions of the short circuit current are accounted for by the separate ions? The likelihood of electrically silent pathways would then be explored. Is the response polarized? The nature of these different transport processes would be examined and quantified. What is the involvement of channel mechanisms and/or carrier-mediated processes? The characteristics of potentially important outward anion transport (kidney and liver-like) systems can and would be determined in this preparation. The preparation would be used to explore how these transporting systems are regulated. Extracellular regulatory pathways would be examined by activating appropriate receptors with neurohormones, mediators and local hormones or neuropeptides to learn the potential role of these substances in influencing secretion. In particular the cyclic nucleotide messenger system would be explored to learn its functional relationship to the vectorial transport pathways for ions. It is also planned to study the transfer of ascorbic acid and glucose. Data obtained from certain kinetic studies of transport would be modeled to several kinetic analyses and compared with past uptake studies when possible. The rate of aqueous humor formation and its composition determine the nutrition of the avascular parts of the eye; the interior cornea, the trabecular meshwork, crystalline lens and probably the anterior vitreous. Therefore this research would bear on certain corneal dystrophies, glaucoma, possibly cataract, and changes in the vitreous with age. Studies of drug mechanisms, e.g., beta adrenergic blockers, would improve the applicant's understanding of the intrinsic mechanisms of aqueous humor formation and help determine how these agents reduce aqueous flow in glaucoma.

描述（改编自申请人的摘要）：此目的建议是学习细胞和分子特征通过研究transepithelial的运输系统进行水性分泌系统横穿眼睛的睫状上皮。一种全新的分离的双层纤毛上皮的膜制备已开发以促进这些研究。该双层的研究将将色素和未色素的单层制剂进行比较也已获得的上皮。生物电特征在这种制备中，跨越电势差，电阻将确定短路电流。电气和示踪剂方法将用于检查离子渗透的机制。为了例如，钠，氯化物和碳酸氢盐对这些细胞制剂及其相互作用的净电流将研究。短路电流的哪个部分是由单独的离子解释？电沉默的可能性然后将探索路径。响应是极化的吗？的本质这些不同的运输过程将被检查和量化。什么通道机制和/或载体介导的过程的参与？潜在重要的向外阴离子运输的特征（肾脏和肝状的）系统可以并且可以在此确定准备。准备工作将用于探索这些方式运输系统受到监管。细胞外调节途径将通过激活适当的受体使用神经激素来检查介体和局部激素或神经肽以学习潜在作用在影响分泌物的这些物质中。特别是循环将探索核苷酸信使系统以学习其功能与离子的矢量传输途径的关系。也是计划研究抗坏血酸和葡萄糖的转移。获得的数据通过某些运输动力学研究将建模到几个动力学分析并在可能的情况下与过去的摄取研究进行了比较。这水性形成及其组成的速率决定了营养眼睛的血管部分；内部角膜，小梁网状工作，结晶镜，可能是前玻璃体。所以这项研究将对某些角膜营养不良，青光眼，可能白内障，并随着年龄的增长而变化。药物研究例如，β肾上腺素能阻断器的机制将改善申请人的了解水幽默形成的内在机制和有助于确定这些药物如何减少青光眼中的水流。