Abstract

The long term objective of this project is to gain insight into the regulation of optic nerve head (ONH) blood flow with varying neural activity, metabolic demand and vasodilator release. This will be achieved with our unique experimental system for quantifying ONH blood flow by laser Doppler flowmetry (LDF) combined with localized chemical measurements with excellent spatial and temporal resolution. Single or double barrel electrochemical microsensors (tips <5 microm) sensitive to nitric oxide (NO), tissue oxygen tension (PO2) or potassium ion (K+) will be used to make measurements in ONH tissue of anesthetized cats. These data will be used to test hypotheses that (1) ONH blood flow, neural activity and 02 metabolism are coupled, (2) NO plays an important role in regulating ONH blood flow, and (3) that the cyclo-oxygenase pathway modulates 02 and NO control of ONH blood flow. The relative importance that local NO, PO2, and K+ play in regulating ONH blood flow will be determined with flickering light stimuli at different frequencies and luminance levels, during increased intraocular pressure, during hypoxia and hypercapnia and following ischemia by temporarily occluding the ophthalmic artery. Regional increases in 02 metabolism with flicker will be quantified from changes in ONH blood flow and PO2. Coupling of ONH blood flow with NO will be assessed by blocking NO synthase. Coupling between ONH blood flow and the cyclo--oxygenase pathway will be determined by blocking with indomethacin. Spatial variations in relationships between ONH blood flow, chemical microenvironment and O2 metabolism will be characterized. ONH blood flow regulation and local chemical responses will be measured for control conditions, after blocking NO synthase, after blocking cyclo-oxygenase, and with both NO synthase and cyclo-oxygenase blocked. These studies are important for understanding how normal ONH blood flow is regulated, and may provide insight into impaired mechanisms with pathological conditions such as glaucoma or neurodegenerative diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009269-06
Application #
2444341
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-05-01
Project End
1998-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Physiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Buerk, Donald G (2007) Nitric oxide regulation of microvascular oxygen. Antioxid Redox Signal 9:829-43
Lamkin-Kennard, Kathleen; Jaron, Dov; Buerk, Donald G (2003) Modeling the regulation of oxygen consumption by nitric oxide. Adv Exp Med Biol 510:145-9
Buerk, Donald G; Lamkin-Kennard, Kathleen; Jaron, Dov (2003) Modeling the influence of superoxide dismutase on superoxide and nitric oxide interactions, including reversible inhibition of oxygen consumption. Free Radic Biol Med 34:1488-503
Buerk, Donald G (2003) Recessed oxygen electrodes: getting more than PO2. Adv Exp Med Biol 510:175-9
Buerk, Donald G; Atochin, Dmitriy N; Riva, Charles E (2003) Investigating the role of nitric oxide in regulating blood flow and oxygen delivery from in vivo electrochemical measurements in eye and brain. Adv Exp Med Biol 530:359-70
Buerk, Donald G; Ances, Beau M; Greenberg, Joel H et al. (2003) Temporal dynamics of brain tissue nitric oxide during functional forepaw stimulation in rats. Neuroimage 18:1-9
Buerk, Donald G; Riva, Charles E (2002) Adenosine enhances functional activation of blood flow in cat optic nerve head during photic stimulation independently from nitric oxide. Microvasc Res 64:254-64
Roy, Arijit; Li, Jinqing; Al-Mehdi, Abu-Bakr et al. (2002) Effect of acute hypoxia on glomus cell Em and psi m as measured by fluorescence imaging. J Appl Physiol 93:1987-98
Buerk, D G (2001) Can we model nitric oxide biotransport? A survey of mathematical models for a simple diatomic molecule with surprisingly complex biological activities. Annu Rev Biomed Eng 3:109-43
Fukumura, D; Gohongi, T; Kadambi, A et al. (2001) Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Proc Natl Acad Sci U S A 98:2604-9

Showing the most recent 10 out of 19 publications