CHOROIDAL AUTOREGULATION AND OCULAR PRESSURE HOMEOSTASIS

  • Kiel, Jeffrey W (PI)

Project: Research project

Project Details

Description

The long-term objective of this project is to systematically investigate
the regulation of choroidal blood flow and the role of the choroid in
ocular pressure homeostasis. Ischemic damage is thought to be the
underlying cause of blindness in ocular diseases such as diabetic
retinopathy and glaucoma. Because the choroid is the primary source of
oxygen and nutrients for the retina, knowledge of choroidal blood flow
regulation is essential for understanding, preventing and treating the
vascular consequences of these diseases. The current view of the choroid
is that it is a passive vascular bed devoid of autoregulatory ability.
However, this conclusion is based on the linear pressure-flow relation
obtained when the perfusion pressure is decreased by raising the
intraocular pressure. Studies in this laboratory show that elevated
intraocular pressure is not the appropriate stimulus to elicit
autoregulation in the choroid, and that choroidal blood flow is well
autoregulated when arterial pressure is the manipulated variable.
Moreover, by controlling the choroidal blood flow (and presumably blood
volume), the mechanism responsible for choroidal autoregulation also
regulates intraocular pressure. Therefore, this project will re-examine
the issue of choroidal blood flow regulation by testing the following
hypotheses: 1) a myogenic mechanism regulates the flow and volume of
blood in the choroid, 2) the myogenic mechanism is modulated by
neurohumoral factors, and 3) the myogenic mechanism plays a significant
role in regulating intraocular pressure. Based on these hypotheses, a
mathematical model of the choroid has been created to serve as the
conceptual framework for the project. Because quantitative information
for many of the model's key variables and relationships is not available
in the literature, verifying the model's qualitative assumptions and
reconciling its inconsistencies provide a logical basis for the project's
specific aims which are: 1) to quantitate the local, neural and humoral
control of choroidal blood flow to determine the normal myogenic
set-point and the physiologic variables that modulate it, 2) to determine
the role of the choroid in intraocular pressure by quantitating the
compliances of the choroid and the ocular chambers, by measuring the
vascular pressure gradients within the choroid, and by determining the
factors that effect choroidal blood volume, and 3) to assess the effect
of ocular hypertension on choroidal blood flow regulation in an animal
model of glaucoma (i.e., trabecular obstruction) and to develop an animal
model of glaucoma by shifting the myogenic set-point. All of the
experiments will be conducted in anesthetized, albino rabbits
artificially respired with room air and appropriately instrumented to
control and monitor arterial and intraocular pressure while measuring
choroidal blood flow by laser-Doppler flowmetry. The results of each
series of experiments will be used to refine the mathematical model so
that upon completion of the project the model will accurately portray the
regulation of choroidal blood .flow and its role in ocular pressure
homeostasis.
StatusFinished
Effective start/end date8/1/923/31/15

Funding

  • National Institutes of Health: $345,060.00
  • National Institutes of Health
  • National Institutes of Health: $372,708.00
  • National Institutes of Health: $338,493.00
  • National Institutes of Health: $130,745.00
  • National Institutes of Health: $355,063.00
  • National Institutes of Health: $285,138.00
  • National Institutes of Health: $292,000.00
  • National Institutes of Health
  • National Institutes of Health: $169,433.00
  • National Institutes of Health: $173,052.00
  • National Institutes of Health: $277,870.00
  • National Institutes of Health: $184,838.00
  • National Institutes of Health: $176,549.00
  • National Institutes of Health: $121,785.00
  • National Institutes of Health: $283,541.00
  • National Institutes of Health
  • National Institutes of Health: $114,183.00

ASJC

  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.