ENDOGENOUS REGULATION OF INTRAOCULAR PRESSURE

眼内压的内源性调节

• 批准号: 6041344
• 负责人: JOHN H LIU
• 金额: $ 36.43万
• 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 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6041344
• 关键词: biological signal transduction; circadian rhythms; clinical research; cortisol; cyclic AMP; enzyme activity; eye disorder chemotherapy; eye disorder diagnosis; glaucoma; hormone regulation /control mechanism; human subject; intraocular fluid; intraocular pressure; melatonin; neuroregulation; ocular hypotensive; protein kinase; radioimmunoassay; saliva; second messengers; sodium potassium exchanging ATPase; sympathetic nervous system; urinalysis; 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（改编自申请人的摘要）：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如何内源性调节在很大程度上尚不清楚。临床观察表明，IOP在一定程度上受中枢神经系统（CNS）调节。中枢神经系统信号如何在体内影响眼组织，特别是在靶细胞内，尚未确定。家兔眼压昼夜节律已被用作研究眼压内源性调节的实验模型。兔眼在暗相时眼压高是由于眼交感神经的激活所致。使用这种夜间IOP升高作为基本模型，将研究睫状突中的体内细胞内信号转导（目的1）。将使用激光照射探测第二信使的水平。将测定蛋白激酶的激活和蛋白磷酸酶的抑制。将测定Na+-K+ ATP酶活性的变化。将使用各种药理学和生理学技术验证这些细胞内事件。由于家兔昼夜IOP节律的同步可能是通过蓝视锥细胞对短波长光的感觉介导的，因此将研究影响夜间IOP升高的传入神经通路（目的2）。还将表征无功能性蓝视锥的兔的昼夜IOP节律。最近，有几项人体研究显示，在黑暗/睡眠阶段出现意外的IOP升高。在严格控制的环境下，将严格检查年轻健康成人的昼夜IOP模式（目标3）。它与光暗周期和睡眠模式的关系将被研究。通过改变出流阻力，阐明了其机理。将检查光谱对夜间IOP的影响。还将描述老年健康成人的昼夜IOP节律。这些多样化方法的共同目标是确定参与IOP调节的内源性机制。这些信息对抗青光眼药物的开发有一定的参考价值。人类研究可能会导致青光眼患者的进一步研究，并可能改进青光眼治疗。