The long term objective of this project is to gain insight into the multiple roles of nitric oxide (NO) in regulating blood flow to the optic nerve head (ONH), coupling of neuronal activity with O2 consumption, and interaction with hypercapnic vasodilation. Potentially damaging roles of NO and peroxynitrite will also be investigated, using tissue nitrosylation as a marker of damage. Single and double barrel NO and PO2 microsensors will be used in the cat eye to measure local chemical concentrations and their variations with varying metabolic demand and with impaired blood flow. A noninvasive optical method of measuring intravascular PO2 in the ONH by phosphorescence quenching will be incorporated into the existing microscope-based infrared laser system for laser Doppler flowmetry (LDF). This will allow simultaneous NO, PO2 and relative red blood cell flux (blood flow) to be measured. Another method for quantifying basal NO levels using hemoglobin trapping with in vivo microdialysis will be used. In vivo microdialysis techniques will also be used to measure other substrates in the vitreous humor near the ONH, and at other sites near the retina, that are relevant to the role of NO in neurotoxic events. These studies are important for understanding how ONH blood flow is regulated under normal physiological conditions, and what conditions can reverse the normally neuroprotective role of NO to one where damage can occur. It is expected that these studies will provide insight into both normal physiological processes and pathological conditions relevant to glaucoma and neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009269-08
Application #
2888383
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-05-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Physiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Buerk, Donald G (2007) Nitric oxide regulation of microvascular oxygen. Antioxid Redox Signal 9:829-43
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
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; 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

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