ENDOGENOUS REGULATION OF AQUEOUS HUMOR DYNAMICS

水液动力学的内源性调节

• 批准号: 3264514
• 负责人: JOHN H LIU
• 金额: $ 21.45万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-11-01 至 1996-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264514
• 关键词: circadian rhythms; corticotropin releasing factor; cyclic AMP; diacylglycerols; dopamine; fluorimetry; glaucoma; growth hormone releasing hormone; hormone regulation /control mechanism; intraocular fluid; intraocular pressure; laboratory rabbit; paraventricular nucleus; prolactin; radioimmunoassay; second messengers; somatostatin; suprachiasmatic nucleus; sympathetic nervous system; thyrotropin releasing hormone

Open-angle glaucoma is associated with an elevated intraocular pressure (IOP) resulting from the disturbance of normal aqueous humor dynamics. Clinical observations indicate that aqueous humor dynamics is regulated to some extent by the central nervous system (CNS through neural and hormonal pathways. However, laboratory data about such actions were either lacking or inconsistent. This project incorporates advanced technology to systematically investigate endogenous neural and hormonal mechanisms in the regulation of aqueous humor dynamics, using the rabbit as a model. Several physiological actions that have profound effects on IOP in conscious rabbits have been identified. Their signal transductions in vivo will be studied in three experimental conditions: circadian change of IOP (Aim 1), electric stimulation o the cervical sympathetic nerves (Aim 2), and endogenous elevation of circulating catecholamines by intravenous injection of thyrotropin releasing hormone (Aim 3). The ocular neurotransmitters and intracellular second messengers (cyclic AMP, diacylglycerol, and inositol 1,4, 5 trisphosphate) mediating the responses will be identified and quantified. Laser irradiation will be use to halt the degradation of intracellular second messengers. Fluorophotometry will be used to measure aqueous flow. The role of the paraventricular nucleus (Aim 4) and the suprachiasmatic nucleus (Aim 5) in the regulation of aqueous humor dynamics in conscious rabbits will be studied by ablation and electric stimulation of these nuclei. CNS neural circuit and efferent pathways will be determined. The interactions between the pituitary hormonal axes and the endogenous mechanisms affecting aqueous humor dynamics (Aim 6) will be clarified after the hormonal axes are activated by administration of pituitary hormone releasing factors: luteinizing hormone releasing hormone, corticotropin releasing factor, and growth hormone releasing hormone. This project will reveal fundamental neural and hormonal mechanisms in the endogenous regulation of aqueous humor dynamics in rabbits. This new knowledge should benefit relevant research in other species and help to refine the rationale for developing more effective antiglaucoma treatment.

开角型青光眼与眼内压升高有关 (IOP)由正常的房水动力学紊乱引起。 临床观察表明，房水动力学是受调节的， 在一定程度上通过中枢神经系统（CNS通过神经和 激素途径 然而，有关此类行为的实验室数据 缺乏或不一致。 该项目采用先进的 系统研究内源性神经和激素技术 机制，在调节水的体液动力学，使用兔 做模特 对IOP有深远影响的几种生理作用， 有意识的兔子被发现了。 它们的信号转导 将在三种实验条件下研究体内：昼夜节律变化 眼内压（Aim 1），颈交感神经电刺激 (Aim 2），和内源性升高循环儿茶酚胺， 静脉注射促甲状腺激素释放激素（Aim 3）。 的 眼神经递质和细胞内第二信使（环AMP， 二酰基甘油和肌醇1，4，5三磷酸）介导的 将确定和量化答复。 激光照射将是 用于阻止细胞内第二信使的降解。 荧光光度法将用于测量房水流量。的作用 室旁核（Aim 4）和视交叉上核（Aim 5） 在清醒家兔的房水动力学调节中， 通过消融和电刺激这些核来研究。 中枢神经系统神经 将确定回路和传出通路。 的相互作用 垂体激素轴和内源性机制之间的联系 影响房水动力学（目标6）将在 通过给予垂体激素激活激素轴 释放因子：促黄体生成素释放激素，促肾上腺皮质激素 释放因子和生长激素释放激素。 这个项目将揭示基本的神经和激素机制 内源性调节兔眼房水动力学。 这 新的知识应该有利于其他物种的相关研究， 完善开发更有效的抗青光眼药物的基本原理 治疗