The overall purpose of this research project is to use newly available technology to study the physiology and pharmacology of blood flow in specific areas of the eye. Special emphasis will be on the role of the sympathetic nervous system in ocular vascular control and on the effects of adrenergic drugs. Previous methodologies, such as microsphere and various washout techniques, are non-continuous and are limited to steady-state flow conditions. The best o f these only produces a """"""""snapshot"""""""" of ocular blood flow at one point in time. We will utilize laser-Doppler flowmetry to measure blood flow from the surface of the eye at the limbus (anterior segment) and at the equator (choroidal flow). A newly developed sensitive transit-time ultrasonic flowmeter will be used to directly measure blood flow from one of the two arteries supplying blood to the front of the eye (long posterior ciliary artery). Both of these methodologies provide a continuous, high-frequency response. Laser-Doppler flowmetry has a high degree spatial resolution, whereas ultrasonic flowmetry will produce more global flow of measurements. Using these techniques, determination of the effects of altered perfusion pressures on regional flow will be determined by experimentally increasing or decreasing both intra-ocular pressure and systemic blood pressure. The degree of regional autoregulation and the role of sympathetic neural input will be determined. Adrenergic drugs (both stimulants and blockers) will be used to systematically define the presence of, and relative roles of adrenergic receptor subtypes in these regional vascular beds. In recent years it has become increasingly clear that disruption of normal circulatory function in the eye may directly cause or exacerbate the pathophysiology of such diverse condition as glaucoma, various retinopathies and macular degeneration. In addition, most of the drugs currently used, or proposed for use, in the treatment of glaucoma have pronounced effects on ocular blood vessels. It is hoped that information gained from this research project will enhance our understanding of ocular physiology and pharmacology in general. More specifically, these results should expand our knowledge of specific adrenergic subtypes in these vascular beds and should prove helpful in the design of new therapeutic agents with greater receptor specificity and fewer untoward side effects.
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