MICROELECTRODE AND BLOOD FLOW STUDIES IN OPTIC NERVE

视神经的微电极和血流研究

• 批准号: 2888383
• 负责人: DONALD G BUERK
• 金额: $ 22.03万
• 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 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888383
• 关键词: cats; eye circulation; glaucoma; hypercapnia; hyperoxia; intraocular fluid; microdialysis; microelectrodes; nitric oxide; optic nerve; oxygen consumption; oxygen tension; peroxynitrites; phosphorescence; reactive hyperemia; retina circulation; statistics /biometry; ultrasound blood flow measurement; vasodilation

DESCRIPTION: The long term objective of this project is to gain insight into the multiple roles of nitric oxide (NO) in regulating blood flow to the optic nerve head (ONH), coupling of neuronal activity with O2 consumption, and interaction with hypercapnic vasodilation. Potentially damaging roles of NO and peroxynitrite will also be investigated, using tissue nitrosylation as a marker of damage. Single and double barrel NO and PO2 microsensors will be used in the cat eye to measure local chemical concentrations and their variations with varying metabolic demand and with impaired blood flow. A noninvasive optical method of measuring intravascular PO2 in the ONH by phosphorescence quenching will be incorporated into the existing microscope-based infrared laser system for laser Doppler flowmetry (LDF). This will allow simultaneous NO, PO2 and relative red blood cell flux (blood flow) to be measured. Another method for quantifying basal NO levels using hemoglobin trapping with in vivo microdialysis will be used. In vivo microdialysis techniques will also be used to measure other substrates in the vitreous humor near the ONH, and at other sites near the retina, that are relevant to the role of NO in neurotoxic events. These studies are important for understanding how ONH blood flow is regulated under normal physiological conditions, and what conditions can reverse the normally neuroprotective role of NO to one where damage can occur. It is expected that these studies will provide insight into both normal physiological processes and pathological conditions relevant to glaucoma and neurodegenerative diseases.

描述：该项目的长期目标是获得洞察力 一氧化氮（NO）在调节血液流动中的多重作用 视神经乳头 (ONH)，神经元活动与 O2 消耗的耦合， 以及与高碳酸血症血管舒张的相互作用。 潜在的破坏性角色 还将使用组织来研究 NO 和过氧亚硝酸盐的含量 亚硝基化作为损伤的标志。 单、双桶NO和PO2 猫眼中将使用微型传感器来测量局部化学物质 浓度及其随不同代谢需求和变化的变化 血流受损。 一种非侵入式光学测量方法 ONH 中的血管内 PO2 通过磷光猝灭将 纳入现有的基于显微镜的红外激光系统 激光多普勒血流计 (LDF)。 这将允许同时进行 NO、PO2 和 待测量的相对红细胞通量（血流量）。 另一种方法 使用体内血红蛋白捕获来定量基础 NO 水平 将使用微透析。 体内微透析技术也将 用于测量 ONH 附近玻璃体液中的其他底物，以及 视网膜附近的其他位点，与 NO 的作用相关 神经毒性事件。 这些研究对于理解 ONH 如何 正常生理条件下血流是受调节的，什么 条件可以将一氧化氮的正常神经保护作用逆转为一种 可能会发生损坏。 预计这些研究将提供见解 分为正常生理过程和病理状态 与青光眼和神经退行性疾病有关。