The long term objective of this project is to achieve a better understanding of the mechanisms controlling blood flow to the optic nerve head (ONH), and factors which might lead to impaired blood flow and nutritional support. To meet this goal, in vivo experimental studies will be conducted in the ONH of anesthetized cats using microelectrodes to measure tissue oxygen, hydrogen ion (pH) and potassium ion. ONH blood flow will be measured by laser Doppler flowmetry (LDF), a new technology which has been successfully applied to blood flow measurements in the capillaries of skin, bone, nasal and intestinal mucosa, kidney, brain, peripheral nerves and other tissues. A modified LDF system developed in our laboratory uses infra-red laser diodes, permitting blood flow measurements to be made in dark adapted eyes. Our laboratory can now combine LDF with electro-chemical microsensors, providing a unique and powerful experimental system to examine local tissue microenvironment with excellent spatial and temporal resolution. Spatial variations in chemical microenvironment (PO2, pH, K+) are expected since the optic nerve has a complex vasculature with separate sources of blood flow from retinal and choroidal circulations. Experiments will be conducted to obtain tissue distributions and gradients for P02, pH, and K+ under normal, control (unstressed) physiological conditions. Changes in chemical microenvironment will be measured for altered physiological conditions, including elevated intraocular pressure and increased neural activity induced by flickering light stimulus. ONH blood flow, P02, pH, and K+ responses to transient physiological stresses including hyperoxia, hypoxia and hypercapnia will be measured for control and altered conditions. ONH blood flow, P02, pH, and K4+ changes will be measured during dark adaptation for control and altered physiological conditions. Relative changes in oxidative metabolism from control conditions will be calculated from steady state blood flow and P02 differences after the above physiological stresses. Many of these studies have never been attempted before. Results are expected to be relevant to glaucoma, diabetic retinopathy and other pathological conditions which contribute to optic nerve atrophy. Information derived from these studies will assist in interpreting LDF measurements, which may eventually provide an improved, noninvasive clinical instrument for early detection of pathological changes in humans.
Showing the most recent 10 out of 19 publications
