MICROELECTRODE AND BLOOD FLOW STUDIES IN OPTIC NERVE

该项目的长期目标是深入了解 不同神经细胞对视神经头血流量的调节 活动、代谢需求和血管扩张剂的释放。这将会实现的 利用我们独特的实验系统，通过 激光多普勒流量计(LDF)与局部化学物质的结合 具有出色的空间和时间分辨率的测量。单人或 双管电化学微型传感器(TIPS&lt；5微米)对 一氧化氮(NO)、组织氧分压(PO2)或钾离子(K+)将 用于对麻醉猫的ONH组织进行测量。这些 数据将被用来检验假设：(1)没有血液流动，神经 活性和O2代谢是耦合的，(2)NO起着重要作用 在调节ONH血流方面；(3)环氧合酶途径 调节02和NO控制ONH的血流。它的相对重要性 局部NO、PO2和K+在调节ONH血流中的作用将是 由不同频率的闪烁光刺激确定 低氧期间眼压升高时的亮度水平 和高碳酸血症以及随后的缺血通过暂时阻断 眼动脉。地区性的02代谢率上升和闪烁将 根据ONH血流量和PO2的变化进行量化。ONH的耦合 通过阻断一氧化氮合酶来评估有无一氧化氮的血流。偶联 ONH血流和环氧合酶途径之间的关系将是 用消炎痛封闭后测定。中国的空间变异 ONH血流量、化学微环境与O2的关系 将描述新陈代谢的特征。ONH血流调节与局部 在以下情况下，将测量控制条件下的化学反应 阻断一氧化氮合酶，在封闭环氧合酶之后，和两者 合酶和环氧合酶被阻断。这些研究对以下方面具有重要意义 了解正常的ONH血流是如何调节的，并可能提供 对病理情况下受损机制的洞察，如 青光眼或神经退行性疾病。

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.