AUTONOMIC CONTROL OF OCULAR BLOOD FLOW

眼血流的自主控制

• 批准号: 2019794
• 负责人: MICHAEL C KOSS
• 金额: $ 13.83万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2019794
• 关键词: autonomic nervous system; blood pressure; cats; chemical stimulation; electrodes; electrostimulus; enzyme inhibitors; eye circulation; eye pharmacology; hemodynamics; innervation; intraocular pressure; neuroregulation; nitric oxide; nitric oxide synthase; parasympathetic nervous system; respiratory gas level; ultrasound blood flow measurement; vasodilatation

Although a variety of experimental approaches have been applied to studies of the eye circulation, the best of previous methodologies are invasive (e.g., clearance techniques) and/or discontinuous (e.g., microspheres) and only produce measurements at single points in time. These techniques have made it difficult to study autonomic control of ocular blood flow as the needed frequency-response and dose-response measurements would require large numbers of experiments and still only produce "snap shots" of the overall response patterns. The purpose of this project is to apply laser-Doppler and ultrasonic flowmetry techniques to study autonomic mechanisms controlling regional ocular blood flows. A primary emphasis is on the role of nitric oxide (NO) in blood flow regulation and in potential relationships between parasympathetic neural control and nitric oxide mechanisms. Laser-Doppler flowmetry will be used for real-time determinations of flood flows from the anterior choroid, retro-laminar portion of the optic nerve, and from the vasa nervorum of the optic tract. Ultrasonic flowmetry will be used for continuous measurements from the long and short posterior ciliary arteries supplying the anterior and posterior aspects of the eye, respectively. Effects of altered blood gas tensions and of potential autoregulatory mechanisms will be studied; the latter by alteration of both intra-ocular pressure and blood pressure. A role of sympathetic innervation also will be determined in selected tissues. The effect of inhibition of NO synthesis will be determined using the NO synthase inhibitor, L-NAME. Similarly, we will investigate the potential role of NO on CO2 responsiveness and in maintaining normal ocular perfusion following an ischemic challenge. A comprehensive series of experiments are designed to systematically study neurogenic vasodilator mechanisms with emphasis on input from the facial nerve and on the possibility that NO is ultimately responsible for ocular vasodilation at the vascular level. A final series of experiments address potential CNS mechanisms involved in neurogenic vasodilator control of the eye circulation. It is becoming increasingly clear that compromised ocular circulation may cause or exacerbate such diverse pathophysiological conditions as glaucoma, various retinopathies and macular degeneration. In addition, many drugs used, or proposed for use, in treating these disease states have pronounced effects on ocular blood vessels. Information gained from this research project may enhance our understanding of the physiology and pharmacology of the ocular circulation and may prove beneficial in development of new therapeutic agents with greater specificity of action and fewer untoward side effects.

尽管已将多种实验方法应用于研究 在眼部循环中，最好的先前方法是侵入性的 （例如，清除技术）和/或不连续（例如，微球）和/或 仅在单个时间点产生测量。 这些技术具有 使研究眼血流的自主控制很难作为 所需的频率响应和剂量反应测量将需要 大量实验，仍然只产生“快照” 总体响应模式。 该项目的目的是应用激光多普勒和超声波 研究控制区域的自主机制的流量指标技术 眼血流。 主要重点是一氧化氮的作用 （否）血流调节和潜在关系 副交感神经控制和一氧化氮机制。 激光多普勒 流量测量将用于实时确定洪水流的 视神经的前脉络脉络膜，重新层次部分，从 视线的VASA神经。 将使用超声流量 为了从长和短后纤毛的连续测量 供应眼睛前部和后方方面的动脉， 分别。 血液张力改变和潜在自动调节的影响 将研究机制；后者通过两种眼内的改变 压力和血压。 同情神经的作用也将 在选定的组织中确定。 抑制NO的效果 合成将使用NO合酶抑制剂L-NAME确定。 同样，我们将研究NO在CO2上的潜在作用 响应能力和维持正常的眼部灌注后 缺血挑战。 一系列全面的实验旨在 系统地研究神经源性血管扩张剂机制，重点是 面部神经的输入以及最终可能是 负责血管水平的眼部血管舒张。 最后系列 实验解决了参与神经源的潜在中枢神经系统机制 血管扩张器控制眼循环。 越来越清楚的是，眼球循环受损 原因或加剧这种多样化的病理生理状况 青光眼，各种视网膜病变和黄斑变性。 此外， 许多药物用于治疗这些疾病状态的药物 对眼血管有明显的影响。 从中获得的信息 该研究项目可能会增强我们对生理学和 眼循环的药理学，可能有益 开发具有更大作用特异性的新治疗剂 较少的副作用。