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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009344-06
Application #
2608622
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-01-01
Project End
1999-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Yu, Yongxin; Koss, Michael C (2005) Rat clonidine mydriasis model: imidazoline receptors are not involved. Auton Neurosci 117:17-24
Yu, Yongxin; Koss, Michael C (2004) Alpha2-adrenoceptors do not mediate reflex mydriasis in rabbits. J Ocul Pharmacol Ther 20:479-88
Koss, M C (2003) Rilmenidine produces mydriasis in cats by stimulation of CNS alpha 2-adrenoceptors. Auton Autacoid Pharmacol 23:51-6
Koss, Michael C (2002) Effects of sympathetic nerve stimulation on long posterior ciliary artery blood flow in cats. J Ocul Pharmacol Ther 18:115-25
Koss, Michael C (2002) Differential neural activation of vascular alpha-adrenoceptors in oral tissues of cats. Eur J Pharmacol 440:53-9
Roberts, Z V; Koss, M C (2001) Nitric oxide regulation of lingual blood flow in the rat. Nitric Oxide 5:271-7
Yu, Y; Kawarai, M; Koss, M C (2001) Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats. Eur J Pharmacol 419:55-9
Kawarai, M; Koss, M C (2001) Sympathetic control of nasal blood flow in the rat mediated by alpha(1)-adrenoceptors. Eur J Pharmacol 413:255-62
Koss, M C (2001) Effects of inhibition of nitric oxide synthase on basal anterior segment ocular blood flows and on potential autoregulatory mechanisms. J Ocul Pharmacol Ther 17:319-29
Koss, M C; Yu, Y (2000) Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats. Gen Pharmacol 35:159-64

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