PHYSIOLOGY OF THE CILIARY EPITHELIAL BILAYER OF THE EYE

眼睛双层睫状上皮的生理学

• 批准号: 3484049
• 负责人: MARVIN L SEARS
• 金额: $ 19.7万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3484049
• 关键词: active transport; ascorbate; basolateral membrane; beta antiadrenergic agent; bicarbonates; biological fluid transport; calcium transporting ATPase; corneal epithelium; cyclic AMP; drug metabolism; electrical potential; electrophysiology; glaucoma; glucose; intracellular transport; intraocular aqueous flow; ion transport; laboratory rabbit; membrane potentials; membrane reconstitution /synthesis; membrane transport proteins; neurohormones; neuropeptides; retinal pigment epithelium; second messengers; tissue /cell culture; trabecular meshwork; uvea ciliary body

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 提议是了解细胞和分子特征 通过研究跨上皮来研究水液分泌的运输系统 穿过眼睛的睫状上皮的运输。 一种全新的类型 分离的双层睫状上皮的膜制备 的开发是为了促进这些研究。 对这个双层的研究将 与着色和非着色的单层制剂进行比较 还获得了上皮细胞。 生物电特性 该制剂的跨上皮电位差、电阻 并确定短路电流。 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、氯化物和碳酸氢盐分别对 这些细胞制剂的净电流及其相互作用 将被研究。 短路电流的分数是多少 由单独的离子来解释？ 电气静音的可能性 然后将探索途径。 反应是否两极分化？ 的性质 这些不同的运输过程将受到检查和量化。 什么 是通道机制和/或载体介导过程的参与吗？ 潜在重要的阴离子向外传输的特征 （类似肾脏和肝脏的）系统可以并且将在此确定 准备。 该准备工作将用于探索这些 运输系统受到监管。 细胞外调节途径 将通过用神经激素激活适当的受体来进行检查， 介质和局部激素或神经肽以了解潜在作用 这些物质影响分泌。 特别是循环 将探索核苷酸信使系统以了解其功能 与离子矢量传输路径的关系。 这也是 计划研究抗坏血酸和葡萄糖的转移。 获得的数据 根据某些运输动力学研究，可以将其建模为几个 动力学分析并在可能的情况下与过去的摄取研究进行比较。 这 房水形成的速度及其成分决定营养 眼睛的无血管部分；角膜内层、小梁 网状结构、晶状体和可能的前玻璃体。 所以 这项研究可能涉及某些角膜营养不良、青光眼 白内障以及玻璃体随年龄的变化。 药物研究 机制，例如β肾上腺素能阻滞剂，将改善申请人的 了解房水形成的内在机制和 帮助确定这些药物如何减少青光眼中的房水流动。