ENDOGENOUS REGULATION OF INTRAOCULAR PRESSURE

眼内压的内源性调节

• 批准号: 2838292
• 负责人: JOHN H LIU
• 金额: $ 27.93万
• 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 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838292
• 关键词: afferent nerve; biological signal transduction; circadian rhythms; cyclic AMP; dark adaptation; enzyme activity; glaucoma; human subject; intraocular fluid; intraocular pressure; laboratory rabbit; lasers; light adaptations; neuroregulation; phosphoprotein phosphatase; protein kinase; radioimmunoassay; second messengers; sleep; sodium potassium exchanging ATPase; sympathetic nervous system; uvea ciliary body

DESCRIPTION (adapted from the applicant's abstract): Primary open-angle glaucoma is associated with an elevated intraocular pressure (IOP). Although lowering IOP has been the only therapeutic means, how IOP is regulated endogenously is largely unclear. Clinical observations indicate that IOP is regulated to some extent by the central nervous system (CNS). How CNS signals affect ocular tissues in vivo, especially inside the target cells, has not been established. The circadian rhythm of IOP in rabbits has been used as an experimental model to study the endogenous regulation of IOP. Rabbit's IOP is high in the dark phase due to the activation of ocular sympathetic nerves. Using this nocturnal IOP elevation as the basic model, in vivo intracellular signal transduction in the ciliary processes will be studied (Aim 1). Levels of second messengers will be probed using laser irradiation. The activation of protein kinases and the inhibition of protein phosphatases will be assayed. Changes in the activity of Na+-K+- ATPase will be determined. These intracellular events will be verified using various pharmacological and physiological techniques. Since the synchronization of the circadian IOP rhythm in rabbits is probably mediated through the sensation of short-wavelength light by the blue cones, the afferent neural pathway affecting the nocturnal IOP elevation will be studied (Aim 2). The circadian IOP rhythm in rabbits without functional blue cones will also be characterized. Recently there have been several human studies showing an unexpected IOP elevation in the dark/sleep phase. Under a strictly controlled environment, the circadian IOP pattern in young healthy adults will be critically examined (Aim 3). Its relationship with the light-dark cycle and the sleep patterns will be studied. Its mechanism via the change of outflow resistance will be clarified. The spectral effects on the nocturnal IOP will be examined. The circadian IOP rhythm in older healthy adults will be characterized as well. The common goal of these diversified approaches is to define the endogenous mechanisms involved in the regulation of IOP. This information should be useful for the development of antiglaucoma medicines. The human studies may lead to further studies in glaucoma patients and possibly a refinement of glaucoma therapy.

描述（改编自申请人摘要）：原发性开角型 青光眼与眼内压（IOP）升高有关。 虽然降低IOP是唯一的治疗手段，但IOP如何降低是一个问题。 内源性调控在很大程度上是不清楚的。 临床观察表明 IOP在一定程度上受中枢神经系统（CNS）调节。 CNS信号如何影响体内眼组织，特别是靶点内的眼组织 细胞，尚未建立。 兔眼内压的昼夜节律 被用作实验模型来研究内源性调节， IOP。 兔眼的眼压在暗相时高，这是由于眼内 交感神经 使用这种夜间IOP升高作为基本模型， 睫状突中的体内细胞内信号转导将是 研究（目标1）。 第二信使的水平将使用激光探测 辐照 蛋白激酶的激活和 将测定蛋白磷酸酶。 Na ~+-K ~+-活性的变化 将测定ATP酶。 这些细胞内事件将得到验证 使用各种药理学和生理学技术。 以来 兔眼内压昼夜节律的同步化可能是通过 通过蓝色视锥细胞对短波长光的感觉， 影响夜间IOP升高的传入神经通路将是 研究（目标2）。 无功能性眼压的兔眼眼压昼夜节律 还将表征蓝色视锥。 最近有几个 人类研究显示在黑暗/睡眠阶段出现意外的IOP升高。 在严格控制的环境下，年轻人的昼夜IOP模式 将对健康成人进行严格检查（目标3）。 之间的关系 将研究光暗周期和睡眠模式。 其机制 通过流出阻力的变化将被阐明。 光谱 将检查对夜间IOP的影响。 眼压昼夜节律 也将表征老年健康成人。 的共同目标 这些多样化的方法是确定所涉及的内源性机制 调节眼压。 这些信息应该是有用的 抗青光眼药物的开发。 人类研究可能会导致 在青光眼患者中的进一步研究， 疗法