MICROENVIRONMENT OF THE RETINA

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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.