MRI Probes for Mapping Retinal Activity In Vivo

  • Louie, Angelique Y, (PI)

Project: Research project

Description

DESCRIPTION: This proposal describes the development of
probes for three-dimensional imaging of retinal activity. These probes are
magnetic resonance imaging (MRI) contrast agents that are sensitive to membrane
potentials. It is the signal from water protons that provides the image in
typical MRI images and contrast agents interact with water to enhance that
signal. In our previous work we have shown that by blocking the interaction of
water with the contrast agent we can "turn off? enhancement, and then
selectively "turn on" enhancement by removing the block. In these previous
experiments we added a blocking group to the contrast agent that is removable
by enzyme cleavage, so that signal enhancement was dependent upon enzyme
cleavage. Based on these results we hypothesize that we can modulate the
ability of an agent to enhance MRI signal by adding a group that is sensitive
to membrane potentials, thus making signal enhancement dependent on membrane
activity. In our research design we propose to:
1) Design and synthesize an agent based on a known optical indicator of
membrane potentials
2) Characterize the ability of the new agent to enhance contrast in cell-free
and cell culture systems.
3) Perform studies leading to the application of the new agents in eyes in
vivo. These studies include determining the optimal route of delivery for the
agent, and its biodistribution in model animal studies. These investigations will ultimately be extended to rodent models of retinal
degeneration to map the loss of retinal activity over time and correlate the
results with those observed by traditional methods. Results of the proposed
studies will provide a noninvasive method to image membrane activity in deep
tissues; this may aid in the early diagnosis of retinal disease. While our
ultimate goal is to apply these agents in studies of macular degeneration,
these agents would be useful for observations of any system in which membrane
signaling activity plays a role.
StatusFinished
Effective start/end date9/30/028/31/06

Funding

  • National Institutes of Health: $148,500.00
  • National Institutes of Health: $148,500.00
  • National Institutes of Health: $148,500.00

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Contrast Media
Retinal Diseases
Three-Dimensional Imaging
Water
Macular Degeneration
Membrane Potentials
Protons
Early Diagnosis
Rodentia
Research Design
Animal Models
Cell Culture Techniques
Membranes
Enzymes

Keywords

  • Medicine(all)