MICROELECTRODE AND BLOOD FLOW STUDIES IN OPTIC NERVE

视神经的微电极和血流研究

• 批准号: 2162875
• 负责人: DONALD G BUERK
• 金额: $ 17.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2162875
• 关键词: MICROELECTRODE; BLOOD; FLOW; STUDIES; OPTIC

The long term objective of this project is to gain insight into the regulation of optic nerve head (ONH) blood flow with varying neural activity, metabolic demand and vasodilator release. This will be achieved with our unique experimental system for quantifying ONH blood flow by laser Doppler flowmetry (LDF) combined with localized chemical measurements with excellent spatial and temporal resolution. Single or double barrel electrochemical microsensors (tips <5 microm) sensitive to nitric oxide (NO), tissue oxygen tension (PO2) or potassium ion (K+) will be used to make measurements in ONH tissue of anesthetized cats. These data will be used to test hypotheses that (1) ONH blood flow, neural activity and 02 metabolism are coupled, (2) NO plays an important role in regulating ONH blood flow, and (3) that the cyclo-oxygenase pathway modulates 02 and NO control of ONH blood flow. The relative importance that local NO, PO2, and K+ play in regulating ONH blood flow will be determined with flickering light stimuli at different frequencies and luminance levels, during increased intraocular pressure, during hypoxia and hypercapnia and following ischemia by temporarily occluding the ophthalmic artery. Regional increases in 02 metabolism with flicker will be quantified from changes in ONH blood flow and PO2. Coupling of ONH blood flow with NO will be assessed by blocking NO synthase. Coupling between ONH blood flow and the cyclo--oxygenase pathway will be determined by blocking with indomethacin. Spatial variations in relationships between ONH blood flow, chemical microenvironment and O2 metabolism will be characterized. ONH blood flow regulation and local chemical responses will be measured for control conditions, after blocking NO synthase, after blocking cyclo-oxygenase, and with both NO synthase and cyclo-oxygenase blocked. These studies are important for understanding how normal ONH blood flow is regulated, and may provide insight into impaired mechanisms with pathological conditions such as glaucoma or neurodegenerative diseases.

该项目的长期目标是深入了解 不同神经元对视神经乳头 (ONH) 血流的调节 活动、代谢需求和血管舒张剂释放。这将实现 使用我们独特的实验系统来量化 ONH 血流 激光多普勒血流计 (LDF) 结合局部化学 具有出色的空间和时间分辨率的测量。单人或 双筒电化学微型传感器（尖端 <5 微米）对 一氧化氮 (NO)、组织氧分压 (PO2) 或钾离子 (K+) 将 用于测量麻醉猫的 ONH 组织。这些 数据将用于检验以下假设：(1) ONH 血流、神经 活性与O2代谢耦合，（2）NO发挥重要作用 调节 ONH 血流，以及 (3) 环加氧酶途径 调节 O2 和 NO 对 ONH 血流的控制。相对重要性 局部NO、PO2和K+在调节ONH血流中的作用是 通过不同频率的闪烁光刺激来确定 亮度水平、眼压升高期间、缺氧期间 和高碳酸血症以及通过暂时闭塞缺血引起的 眼动脉。 02 新陈代谢的区域性增加会伴随闪烁 通过 ONH 血流量和 PO2 的变化进行量化。 ONH耦合 通过阻断 NO 合酶来评估含 NO 的血流。耦合 ONH 血流和环加氧酶途径之间的关系 用吲哚美辛封闭测定。空间变化 ONH血流、化学微环境和O2之间的关系 代谢将被表征。 ONH血流调节和局部 化学反应将在控制条件下测量，之后 阻断环加氧酶后阻断 NO 合酶，并同时使用 NO 合酶和环加氧酶被阻断。这些研究对于 了解正常 ONH 血流是如何调节的，并可能提供 深入了解病理条件下的受损机制，例如 青光眼或神经退行性疾病。