Although a variety of experimental approaches have been applied to studies of the eye circulation, the best of previous methodologies are invasive (e.g., clearance techniques) and/or discontinuous (e.g., microspheres) and only produce measurements at single points in time. These techniques have made it difficult to study autonomic control of ocular blood flow as the needed frequency-response and dose-response measurements would require large numbers of experiments and still only produce """"""""snap shots"""""""" of the overall response patterns. The purpose of this project is to apply laser-Doppler and ultrasonic flowmetry techniques to study autonomic mechanisms controlling regional ocular blood flows. A primary emphasis is on the role of nitric oxide (NO) in blood flow regulation and in potential relationships between parasympathetic neural control and nitric oxide mechanisms. Laser-Doppler flowmetry will be used for real-time determinations of flood flows from the anterior choroid, retro-laminar portion of the optic nerve, and from the vasa nervorum of the optic tract. Ultrasonic flowmetry will be used for continuous measurements from the long and short posterior ciliary arteries supplying the anterior and posterior aspects of the eye, respectively. Effects of altered blood gas tensions and of potential autoregulatory mechanisms will be studied; the latter by alteration of both intra-ocular pressure and blood pressure. A role of sympathetic innervation also will be determined in selected tissues. The effect of inhibition of NO synthesis will be determined using the NO synthase inhibitor, L-NAME. Similarly, we will investigate the potential role of NO on CO2 responsiveness and in maintaining normal ocular perfusion following an ischemic challenge. A comprehensive series of experiments are designed to systematically study neurogenic vasodilator mechanisms with emphasis on input from the facial nerve and on the possibility that NO is ultimately responsible for ocular vasodilation at the vascular level. A final series of experiments address potential CNS mechanisms involved in neurogenic vasodilator control of the eye circulation. It is becoming increasingly clear that compromised ocular circulation may cause or exacerbate such diverse pathophysiological conditions as glaucoma, various retinopathies and macular degeneration. In addition, many drugs used, or proposed for use, in treating these disease states have pronounced effects on ocular blood vessels. Information gained from this research project may enhance our understanding of the physiology and pharmacology of the ocular circulation and may prove beneficial in development of new therapeutic agents with greater specificity of action and fewer untoward side effects.
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