CHOROIDAL AUTOREGULATION AND OCULAR PRESSURE HOMEOSTASIS

脉络膜自动调节和眼压稳态

• 批准号: 2701393
• 负责人: Jeffrey W Kiel
• 金额: $ 13.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701393
• 关键词: autonomic nervous system; biological models; blood volume; cats; choroid uvea; eye pharmacology; glaucoma; homeostasis; intraocular pressure; laboratory rabbit; mathematical model; neuropharmacology; retina circulation; sympathetic nervous system; ultrasound blood flow measurement; vascular smooth muscle; vascular smooth muscle nervous control; vasoconstrictors

The long-term objective of this project is to systematically investigate the regulation of choroidal blood flow and the role of the choroid in ocular pressure homeostasis. Ischemic damage is thought to be the underlying cause of blindness in ocular diseases such as diabetic retinopathy and glaucoma. Because the choroid is the primary source of oxygen and nutrients for the retina, knowledge of choroidal blood flow regulation is essential for understanding, preventing and treating the vascular consequences of these and other diseases. In contrast to the previous view of the choroid as a passive vascular bed devoid of autoregulatory ability, studies during the past funding period show that choroidal blood flow is well autoregulated, particularly when arterial pressure is the manipulated variable. Moreover, the results indicate that the mechanism responsible for choroidal autoregulation is myogenic rather than metabolic (as in the retina), and that it acts to control choroidal blood volume and so minimize the fluctuations in intraocular pressure that would otherwise occur during normal variations in arterial blood pressure. The present project will continue to examine the regulation of choroidal blood flow by testing the following hypotheses: 1) a myogenic mechanism regulates the flow and volume of blood in the choroid, 2) the myogenic mechanism is modulated by neurohumoral factors, and 3) the myogenic mechanism plays a significant role in intraocular pressure homeostasis. A mathematical model based on these hypotheses serves as the conceptual framework for the project and as a dynamic 'library' for the project's results. Although the model was refined significantly during the last funding period, quantitative information for many of the model's key variables and relationships must still be obtained. To achieve this goal, the project's specific aims are: 1) to quantitate the neural and humoral control of choroidal blood flow to determine the normal myogenic set-point and the physiologic variables that modulate it, and 2) to determine the role of the choroid in intraocular pressure by determining the factors that affect choroidal blood volume. The work will be conducted in anesthetized animals instrumented to control and monitor arterial and intraocular pressures while measuring choroidal blood flow by laser-Doppler flowmetry. Most of the experiments will involve the systematic manipulation of arterial and intraocular pressures before and after selective blockade or stimulation of known vascular effector systems to quantify their effects on the choroidal pressure-flow relation and intraocular pressure. The experimental results will be used to continue refining the mathematical model so that the model accurately portrays the regulation of choroidal blood flow and its role in ocular pressure homeostasis upon completion of the project.

该项目的长期目标是系统地调查 脉络膜血流的调节和脉络膜在 眼压体内平衡。缺血性损害被认为是 眼部疾病（例如糖尿病）失明的根本原因 视网膜病和青光眼。因为脉络膜是 视网膜的氧气和养分，脉络膜血流的知识 监管对于理解，防止和治疗至关重要 这些疾病和其他疾病的血管后果。与 脉络膜的先前视图是被动血管床 自动调节能力，过去的资金期间的研究表明 脉络膜血流受到很好的自动调节，尤其是在动脉 压力是操纵变量。 此外，结果表明 负责脉络膜自动调节的机制是肌原样的 比代谢（如在视网膜中），并且可以控制脉络膜 血液体积，从而最大程度地减少眼内压中的波动 否则将在动脉血压正常变化期间发生。 本项目将继续检查脉络膜的调节 通过测试以下假设的血液流动：1）肌源性机制 调节脉络膜中血液的流量和数量，2）肌原性 机理由神经肿瘤因子调节，3）肌原性 机制在眼内压体内平衡中起着重要作用。一个 基于这些假设的数学模型可作为概念 该项目的框架，作为项目的动态“库” 结果。 尽管该模型在最后一次是显着完善的 资金期，许多模型关键的定量信息 仍然必须获得变量和关系。为了实现这一目标， 该项目的具体目的是：1）定量神经和体液 控制脉络膜血流以确定正常的肌源定点 以及调节它的生理变量，2）确定 通过确定因素 影响脉络膜血容量。 这项工作将在麻醉中进行 仪器以控制和监测动脉和眼内的动物 通过激光多普勒流量指定测量脉络膜血流的压力。 大多数实验将涉及系统的操纵 选择性封锁之前和之后的动脉和眼内压力或 刺激已知的血管效应系统，以量化其对 脉络膜压力流的关系和眼内压。这 实验结果将用于继续完善数学 模型使模型准确地描绘了脉络膜的调节 血流及其在完成时在眼压稳态中的作用 项目。