Continuous measurement and control of intraocular pressure in normal and glaucomatous eyes

项目摘要 眼内压（IOP）的调节是一个相当大的科学、临床和药学的主题。 兴趣高眼压是青光眼的一个确定的危险因素，青光眼是一种隐性疾病， 杀死视网膜神经节细胞，因此降低IOP是目前所有治疗的主要焦点。第一种方法 在临床护理中，给患者开药的目的是改变患者体内水状流体的产生和流出， 眼睛这些药物中的许多通过靶向来自自主神经的信号来实现治疗效果 系统，其动态地调节房水动力学，原因尚不完全清楚。 最强的调节器之一是大脑中的视交叉上核， 平均IOP节律。其他自主神经调节剂包括应激和颅内压（ICP）。他们的 集体行动导致IOP持续波动，有时达到导致青光眼的水平 在某些个体中，如果维持较长的时间。ICP参与IOP调节， 有趣的是，ICP有助于跨视神经乳头的跨椎板压力梯度， 确定视网膜神经节细胞轴突在离开时所经历的机械应力和应变分布 眼睛到大脑。因此，ICP也可能是青光眼病理生理学的因素。 这项研究旨在促进我们对昼夜节律和自主机制的理解 IOP调节的机制以及这些机制在疾病发作和进展中的潜在参与。到 为此，使用独一无二的技术，为研究人员提供记录或控制IOP的能力， 大鼠24小时颅内压。IOP、ICP、体温、自发活动、房水流出功能，以及 当环境光-暗循环时， 施用改变的交感神经激动剂和拮抗剂， 暂时应用于眼睛。从而对眼神经的起源和控制有了新的认识 节律，ICP对IOP的传出控制，以及昼夜节律和自主神经系统的可能作用 在青光眼中。这些见解可能会导致疾病治疗的新方法和目标。

PROJECT SUMMARY Regulation of intraocular pressure (IOP) is a subject of considerable scientific, clinical, and pharmaceutical interest. High IOP is an established risk factor for glaucoma, an insidious disease that causes blindness by killing retinal ganglion cells, so lowering IOP is a primary focus of all current treatments. The first approach in clinical care is to prescribe patients medicines that alter the production and outflow of aqueous fluid in the eye. Many of these medicines achieve a therapeutic effect by targeting signals from the autonomic nervous system, which dynamically modulates aqueous humor dynamics for reasons that are not entirely known. One of the strongest modulators is the suprachiasmatic nucleus in the brain, which coordinates a circadian rhythm in mean IOP. Other autonomic neuromodulators include stress and intracranial pressure (ICP). Their collective actions cause IOP to fluctuate continually, sometimes reaching levels that would cause glaucoma in some individuals if maintained for extended periods. Involvement of ICP in IOP modulation is particularly intriguing because ICP contributes to the translaminar pressure gradient across the optic nerve head, which determines the mechanical stress and strain profiles experienced by retinal ganglion cell axons as they exit the eye to the brain. ICP could therefore factor into glaucoma pathophysiology as well. The proposed research is directed at advancing our understanding of circadian and autonomic mechanisms of IOP modulation and the potential involvement of these mechanisms in disease onset and progression. To do this, one-of-a-kind technologies are used that provide researchers the ability to record or control IOP or ICP round-the-clock in rats. IOP, ICP, body temperature, locomotor activity, aqueous outflow facility, and ocular compliance will be concurrently recorded in various combinations as ambient light-dark cycle is altered, sympathetic nerve agonists and antagonists are administered, and variable pressure loads are transiently applied to the eye. In so doing, new insights will be gained about the origin and control of ocular rhythms, about efferent control of IOP by ICP, and about possible roles of circadian and autonomic systems in glaucoma. These insights could lead to new approaches and targets for disease treatment.