PATHOGENESIS OF GLAUCOMATOUS CUPPING--NO, O2 &PERICYTES

  • Anderson, Douglas, (PI)

Project: Research project

Description

The blood flow in the optic nerve head is normally autoregulated, little
affected by the level of intraocular pressure (IOP). Such regulation may
be achieved through response to tissue levels of oxygen and carbon
dioxide, which reflect the balance between local tissue metabolism and
the volume of local blood flow. Hypothetically in glaucoma this
regulation is faulty in the optic nerve head, permitting ischemic damage
when the circulation is challenged by elevation of IOP. Only a little is know of the local physiologic event by which
autoregulations is achieved, but nothing about how it may become faulty,
or how faulty autoregulation might be corrected. Vascular smooth muscle
of arteries and arterioles and precapillary sphincters have considerable
influence on distribution of blood flow to various tissue regions. We
hypothesize that capillaries may provide local fine tuning of blood flow,
at least in some tissues, and specially in the optic nerve and retina,
and perhaps the rest of the central nervous system. If capillaries participate in local control of blood flow, it may be
achieved through pericytes, contractile cells whose function is not
known, found in the walls of capillaries, especially in the central
nervous system, including retina and optic nerve. Pericyte contractile
or relaxation response to changes in local oxygen tension, mediated
through nitric oxide and other mediators, may permit local influence on
blood flow in capillaries. Responses to carbon dioxide, pH, adenosine
accumulation, and other local chemical changes may also participate in
capillary autoregulation of blood flow. In this project we plan to study the relaxation responses of pericytes
grown in cell culture to endothelium-derived relaxing factor (EDRF),
identified as nitric oxide (NO), and the modification of NO-induced
relaxation by oxygen tension (pO2). Responses to be observed are cell
contraction, changes in intracellular free calcium concentration,
production of nitrite degradation products of NO, and changes in
adenylate cyclase activity.
StatusFinished
Effective start/end date1/1/9412/31/97

Funding

  • National Institutes of Health: $135,070.00
  • National Institutes of Health
  • National Institutes of Health: $125,390.00

Fingerprint

Pericytes
Nitric Oxide
Optic Disk
Optic Nerve
Oxygen
Intraocular Pressure
Homeostasis
Retina
Endothelium-Dependent Relaxing Factors
Carbon Dioxide
Arterioles
Nitrites
Blood Volume
Central Nervous System
Glaucoma
Arteries
Cell Culture Techniques
Calcium
Blood Vessels

ASJC

  • Medicine(all)