MICROELECTRODE AND BLOOD FLOW STUDIES IN OPTIC NERVE

该项目的长期目标是深入了解 调节视神经乳头（ONH）血流与不同的神经 活动、代谢需求和血管扩张剂释放。完成这项工作的方法是 通过我们独特的实验系统定量ONH血流， 激光多普勒血流仪（LDF）结合局部化学 测量具有出色的空间和时间分辨率。单个或 双筒式电化学微传感器（尖端<5微米）， 一氧化氮（NO）、组织氧张力（PO2）或钾离子（K+）将 用于在麻醉猫的ONH组织中进行测量。这些 数据将用于检验以下假设：（1）ONH血流，神经 活性和O2代谢是耦合的，（2）NO起重要作用 在调节ONH血流中，以及（3）环加氧酶途径 调节ONH血流的O2和NO控制。的相对重要性 局部NO、PO2和K+在调节ONH血流中的作用将是 用不同频率的闪烁光刺激测定， 亮度水平，眼内压升高期间，缺氧期间 和高碳酸血症以及缺血后通过暂时阻塞 眼动脉在闪烁的情况下，O2代谢的区域性增加将 通过ONH血流和PO2的变化进行定量。ONH偶联 通过阻断NO合酶来评估具有NO的血流。耦合 ONH血流和环加氧酶通路之间的联系 通过用吲哚美辛阻断来测定。的空间变化 ONH血流量、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 将测量对照条件下的化学反应， 阻断NO合酶，阻断环氧合酶后， 合酶和环氧合酶被阻断。这些研究对于 了解正常的ONH血流是如何调节的， 深入了解受损机制与病理条件，如 青光眼或神经变性疾病。

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.