Ocular blood flow and intraocular pressure homeostasis

眼血流量和眼压稳态

• 批准号: 7452337
• 负责人: Jeffrey W Kiel
• 金额: $ 27.79万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7452337
• 关键词: Address; Affect; Anterior; Aorta; Behavior; Blood Vessels; Blood Volume; Blood flow; Blood-Aqueous Barrier; Cannulas; Choroid; Ciliary Body; Condition; Control Animal; Data; Development; Drug usage; Endothelin; Equilibrium; Excision; Eye; Fiber Optics; Fluorophotometry; Funding; Gastric mucosa; Glaucoma; Goals; Homeostasis; Inferior vena cava structure; Knowledge; Laboratories; Laser-Doppler Flowmetry; Liquid substance; Measurement; Measures; Metabolic; Metabolism; Modality; Modeling; Movement; Nitric Oxide; Ocular Hypertension; Oryctolagus cuniculus; Perfusion; Pharmaceutical Preparations; Pharmacology; Physiologic Intraocular Pressure; Physiology; Production; Protocols documentation; Range; Rate; Regulation; Risk Factors; Role; Sclera; Standards of Weights and Measures; Sturnus vulgaris; Techniques; Testing; Thinking; Tissues; Vasodilation; Venous Pressure level; Work; aqueous; base; concept; in vivo; instrument; mathematical model; novel; pressure; research study; vasoconstriction; wasting

DESCRIPTION (provided by applicant): Ocular hypertension is the most significant risk factor for glaucoma, and lOP reduction remains the primary goal of glaucoma treatment. The steady state lOP is set by aqueous production and outflow, and it is our knowledge of aqueous dynamics that provides a rational basis for understanding ocular hypertension and the various treatment modalities used to manipulate lOP. The goal of this project is to address a fundamental gap in our knowledge of aqueous dynamics: the role of ciliary blood flow in aqueous production. The project will test the hypothesis that a critical level of ciliary perfusion exists for a given level of secretory stimulation, and that aqueous production is blood flow independent until blood flow is reduced below that critical level. The project's specific aims are to quantify the interrelationships between ciliary blood flow, metabolism, and aqueous production over a wide range of perfusion pressures under control conditions and after administration of drugs expected to alter aqueous production or ciliary blood flow, or both. The experiments will be performed in anesthetized rabbits instrumented with hydraulic occluders on the inferior vena cava and aorta to control mean arterial pressure (MAP), which will be measured via an arterial cannula. The eye will be cannulated to measure lOP. Ciliary blood flow will be measured by laser Doppler flowmetry using a fiber optic probe placed on the sclera over the ciliary body. Ciliary metabolism will be estimated from ciliary PO2 measurements. Episcleral and anterior uveal venous pressures will be measured by the servonull technique. Aqueous production will be measured by fluorophotometry. The standard protocol will entail changing ciliary blood flow by holding the MAP at different levels above and below baseline for 60-90 min to obtain steady state measurements. The protocol will be performed initially in control animals to establish the normal relationships between the measured variables, and then under conditions of drug-induced secretory stimulation and inhibition, and ciliary vasodilation and vasoconstriction. Plotting the aqueous flow as a function of ciliary blood flow will indicate which drugs alter aqueous production directly at the cellular level, those that affect production indirectly due to their vascular effects, and those that affect production directly and indirectly. This information will further our understanding of the physiology of aqueous dynamics and the pharmacology of drugs used in the treatment of glaucoma, and will also be used to continue the development of a comprehensive mathematical model of ocular hydrodynamics.

描述（由申请人提供）：眼高血压是青光眼最重要的危险因素，而LOP减少仍然是青光眼治疗的主要目标。稳态LOP是由水性生产和流出设定的，我们对水性动力学的了解为理解眼高血压和操纵LOP的各种治疗方式提供了合理的基础。该项目的目的是解决我们对水性动力学知识的根本差距：睫状血流在水性生产中的作用。该项目将检验以下假设：对于给定的分泌刺激，存在睫状灌注的临界水平，并且水的产生是血流独立的，直到血液流量降低到低于该临界水平以下。该项目的具体目的是量化在控制条件下的各种灌注压力以及预期改变水性产生或睫状血流的药物后，睫状血流，代谢和水性产生之间的相互关系。实验将在下腔静脉和主动脉上用液压阻塞的麻醉兔子进行，以控制平均动脉压（MAP），该动脉压（MAP）将通过动脉插管进行测量。眼睛将插管以测量LOP。睫状血流将通过激光多普勒流动仪测量，使用放置在纤毛体上的巩膜上的光纤探针。睫状代谢将从睫状PO2测量中估算。 servonull技术将测量粘液剂和前紫外静脉压力。水生产将通过荧光测量法测量。标准方案将通过将地图固定在基线上方和低于基线的不同水平60-90分钟以获得稳态测量值来改变睫状血流。该方案最初将在对照动物中执行，以建立测量变量之间的正常关系，然后在药物诱导的分泌刺激和抑制条件下以及睫状血管舒张和血管收缩。绘制水流作为睫状血流的函数将表明哪些药物直接在细胞水平上改变水性产生，而这些药物由于其血管作用而间接影响生产的药物，以及直接和间接影响生产的药物。这些信息将进一步了解我们对青光眼治疗水性动力学的生理学和药物的生理学，还将用于继续开发眼部流体动力学的综合数学模型。