Aqueous Humor Outflow Control and Intraocular Pressure

房水流出控制和眼压

• 批准号: 6365137
• 负责人: MORTIMER MORDECAI CIVAN
• 金额: $ 39.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2004-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6365137
• 关键词: adenosine; cell morphology; flow cytometry; glaucoma; human tissue; inflammation; intraocular aqueous flow; intraocular pressure; ion transport; laboratory mouse; molecular cloning; particle counter; polymerase chain reaction; purinergic receptor; sclera; trabecular meshwork; video microscopy; voltage /patch clamp

DESCRIPTION (provided by applicant): The proposed research involves integrating membrane physiology and a novel method of measuring intraocular pressure in the mouse to address the mechanisms of aqueous humor outflow and intraocular pressure. Cell swelling within the trabecular meshwork (TM) and Schlemm's canal (SC) decreases the aqueous humor outflow facility (C), and cell shrinkage within this small region increases C. Subtype-specific adenosine agonists have also been reported to alter outflow. On the basis of published evidence and our own data, we propose that: (1) TM-cell swelling directly and indirectly modulates outflow; (2) SC-cell swelling also alters the resistance to flow across the SC inner wall; (3) adenosine and ATP receptors modulate cell volume regulation of TM and SC cells; (4) the mechanisms and/or regulation of cell volume control are different in TM and SC cells; and (5) the novel application of servo-null micropipette technology to measure IOP in the mouse will permit direct extension of the membrane physiology to in vivo physiology. The program provides an unusual opportunity for integrating cellular and whole-animal techniques in developing novel pharmacologic interventions for reducing intraocular pressure (IOP) in treating glaucoma and in studying targeted genetic mouse models of aqueous humor outflow. The specific aims are to: (1) Identify the mechanisms and regulation of cell volume control of human TM and SC cells and immortalized mouse TM cells; (2) Determine the actions and identity of the purinergic receptors and ectoenzymes responsible for modulating the cell volume mechanisms and regulations in these cells; and (3) Extend the cell studies to analysis of aqueous humor dynamics with the servo-null micropipette system (SNMS) we have developed, which provides the first and only reliable approach for measuring IOP in the mouse.

描述（由申请人提供）：拟议的研究涉及整合 膜生理学和测量眼压的新方法 小鼠解决房水流出和眼内机制 压力。小梁网 (TM) 和施累姆氏管内的细胞肿胀 (SC) 减少房水流出设施 (C) 和细胞收缩 在这个小区域内增加 C. 亚型特异性腺苷激动剂 据报道也改变了流出量。根据已发表的证据和我们的 根据自己的数据，我们提出：（1）TM细胞直接和间接肿胀 调节流出； (2) SC 细胞肿胀也会改变流动阻力 穿过 SC 内壁； (3)腺苷和ATP受体调节细胞体积 TM 和 SC 细胞的调节； (4)细胞的机制和/或调节 TM 和 SC 细胞的音量控制不同； (5)新颖的应用 零伺服微量移液器技术测量小鼠眼压将允许 膜生理学直接延伸到体内生理学。该计划 为整合细胞和整个动物提供了一个不寻常的机会 开发新的药物干预技术以减少 眼压（IOP）在治疗青光眼和研究靶向治疗中的作用 房水流出的遗传小鼠模型。 具体目标是： (1) 明确细胞的机制和调控 人TM和SC细胞以及永生化小鼠TM细胞的体积控制； (2) 确定嘌呤能受体和胞外酶的作用和身份 负责调节这些细胞的体积机制和调节 细胞； (3) 将细胞研究扩展到房水动力学分析 使用我们开发的伺服零微量移液器系统（SNMS）， 提供了第一个也是唯一可靠的测量小鼠眼压的方法。