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

项目总结 眼内压(IOP)的调节是一个相当多的科学、临床和药学课题。 利息。高眼压是青光眼的既定危险因素，青光眼是一种潜在的疾病，通过以下方式导致失明 杀死视网膜神经节细胞，因此降低眼压是目前所有治疗方法的主要重点。第一种方法 在临床护理中，给患者开出改变房水产生和流出的药物。 眼睛。这些药物中的许多是通过靶向自主神经的信号来达到治疗效果的 该系统动态调节房水动力学，其原因尚不完全清楚。 最强的调节器之一是大脑中的视交叉上核，它协调昼夜节律 平均眼压的节律。其他自主神经调节剂包括压力和颅内压(ICP)。他们的 集体行动会导致眼压持续波动，有时会达到会导致青光眼的水平 在一些个体中，如果维持较长的时间。尤其是颅内压在眼压调节中的作用 耐人寻味的是，因为颅内压有助于视神经头的跨层压力梯度，这是 确定视网膜神经节细胞轴突退出时所经历的机械应力和应变分布 从眼睛到大脑。因此，颅内压也可以影响青光眼的病理生理学。 拟议的研究旨在促进我们对昼夜节律和自主神经机制的理解。 眼压调节以及这些机制在疾病发生和发展中的潜在参与。至 为此，使用了一种独一无二的技术，为研究人员提供了记录或控制眼压或 大鼠全天候颅内压监测。眼压、颅内压、体温、活动能力、房水流出设施以及 眼睛顺应性将以各种组合同时记录，因为环境光-暗周期是 应用改变的交感神经激动剂和拮抗剂，并施加可变压力负荷 暂时涂在眼睛上。通过这样做，将获得关于眼睛的起源和控制的新的见解 节律，关于颅内压对眼压的传出控制，以及关于昼夜节律和自主神经系统的可能作用 青光眼。这些见解可能会为疾病治疗带来新的方法和目标。

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.