title: Applications of azo-based probes for imaging retinal hypoxia.
abstract: We report the design and synthesis of an activatable molecular imaging probe to detect hypoxia in mouse models of retinal vascular diseases. Hypoxia of the retina has been associated with the initiation and progression of blinding retinal vascular diseases including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. In vivo retinal imaging of hypoxia may be useful for early detection and timely treatment of retinal diseases. To achieve this goal, we synthesized HYPOX-3, a near-infrared (NIR) imaging agent coupled to a dark quencher, Black Hole Quencher 3 (BHQ3), which has been previously reported to contain a hypoxia-sensitive cleavable azo-bond. HYPOX-3 was cleaved in hypoxic retinal cell culture and animal models, enabling detection of hypoxia with high signal-to-noise ratios without acute toxicity. HYPOX-3 fluorescences in hypoxic cells and tissues and was undetectable under normoxia. These imaging agents are promising candidates for imaging retinal hypoxia in preclinical disease models and patients.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
authors.forename: Md Imam
authors.initials: MI
authors.lastname: Uddin
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Craft
authors.affiliation: A. B. Hancock, Jr., Memorial Laboratory for Cancer Research, Department of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute of Chemical Biology, Center for Molecular Toxicology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.affiliation: A. B. Hancock, Jr., Memorial Laboratory for Cancer Research, Department of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute of Chemical Biology, Center for Molecular Toxicology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States ; Molecular Physiology and Biophysics, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
authors.forename: Ashwath
authors.initials: A
authors.lastname: Jayagopal
keywords: Hypoxia; imaging agents; molecular imaging; retina; retinal hypoxia; retinal imaging