Hypoxia has been associated with
retinal diseases which lead the
causes of irreversible vision loss, including diabetic retinopathy,
retinopathy of prematurity, and age-related macular degeneration.
Therefore, technologies for imaging hypoxia in the retina are needed
for early disease detection, monitoring of disease progression, and
assessment of therapeutic responses in the patient. Toward this goal,
we developed two hypoxia-sensitive imaging agents based on nitroimidazoles
which are capable of accumulating in hypoxic cells in vivo. 2-nitroimidazole
or Pimonidazole was conjugated to fluorescent dyes to yield the imaging
agents HYPOX-1 and HYPOX-2. Imaging agents were characterized in cell
culture and animal models of retinal vascular diseases which exhibit
hypoxia. Both HYPOX-1 and -2 were capable of detecting hypoxia in
cell culture models with >10:1 signal-to-noise ratios without acute
toxicity. Furthermore, intraocular administration of contrast agents
in mouse models of retinal hypoxia enabled ex vivo detection of hypoxic
tissue. These imaging agents are a promising step toward translation
of hypoxia-sensitive molecular imaging agents in preclinical animal
models and patients.
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