MICROENVIRONMENT OF THE RETINA

本申请中提出的实验旨在研究 完整的视网膜麻醉猫的微环境， 氧气的正常输送和利用，以及 以及对氧气输送障碍的可能治疗。本地测量 氧气，葡萄糖和血液流动的微电极将在 视网膜或视网膜附近的玻璃体中。 视网膜电图 将被记录为视网膜功能状态的指标。 在 其它实验将记录脉络膜血流。 的优点 这种制剂的优点是， 关系可以保持。 本课题分为以下几个部分：1）神经网络的影响 （交感神经和副交感神经）调节脉络膜 将确定远端视网膜的氧合循环。2)一 一种可测量葡萄糖的葡萄糖敏感微电极 将开发远端视网膜中的浓度，以便 评估糖酵解对能量代谢的贡献， 完整的视网膜，并研究糖酵解的变化，在光明和黑暗 适应和低氧血症期间。3)一种用于测量局部 视网膜血流，使用氢作为示踪剂，将被开发， 用于研究负责正常调节的机制， 视网膜循环的微脉管系统中的血流。4)在 将进行体外研究，以了解机制， 全氟化碳人造血液替代品 增加视网膜氧分压。5)一种新的实验方法 可逆性视网膜阻塞期间的视网膜氧合将 开发和使用。6)长期实验的后果 视网膜缺氧（眼内压中度升高） 代谢和电功能将被研究，作为一种手段， 评估视网膜缺氧本身在疾病中的作用。 预计这些研究将与几种疾病相关， 循环系统疾病，包括血管闭塞性疾病、青光眼 以及其他代谢成分被认为是重要的， 如糖尿病性视网膜病。 猫将是动物的选择， 这些研究，因为它的视网膜和视网膜的相似性， 与人类的血管系统相似。 对于这项工作，将没有 使用灵长类动物的显著优势。

The experiments proposed in this application are designed to investigate the micro-environment of the intact retina anesthetized cats with regard to the normal delivery and utilization of oxygen, and the consequences and possible treatment of imppaired oxygen delivery. Local measurements of oxygen, glucose and blood flow will be made with microelectrodes in the retina or in the vitreous near the retina. The electroretinogram will be recorded as an index of the functional state of the retina. In other experiments choroidal blood flow will be recorded. The advantage of this preparation is that normal circulation and physiological relationships can be preserved. The project has several portions: 1) The influence of neural (sympathetic and parasympathetic) regulation of the choroidal circulation on oxygenation of the distal retina will be determined. 2) A glucose-sensitive microelectrode capable of measuring glucose concentration in the distal retina will be developed in order to evaluate the contribution of glycolysis to energy metabolism in the intact retina, and to study changes in glycolysis during light and dark adaptation and during hypoxemia. 3) A technique for measuring local retinal blood flow, using hydrogen as a tracer, will be developed and used to study the mechanisms responsible for the normal regulation of blood flow in the microvasculature of the retinal circulation. 4) In vitro studies will be performed in order to understand the mechanisms by which perfluorocarbon artificial blood substitutes are capable of increasing retinal oxygen tension. 5) A new experimental method to study retinal oxygenation during reversible retinal occlusion will be developed and used. 6) The consequences of long term experimental hypoxia (moderate elevation of intraocular pressure) on retinal metabolism and electrical function will be studied, as a means of assessing the role that retinal hypoxia itself may play in disease. These studies are expected to be relevant for several diseases with circulatory components, including vascular occlusive diseases, glaucoma and others in which a metabolic component is thought to be important, such as diabetic retinopathy. The cat will be the animal of choice for these studies, because of the similarity of its retina and its retinal vasculature to those in humans. For this work, there would be no significant advantage in using primates.