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Ashwath Jayagopal, Chauca Moore; In Vivo Imaging of RNA Biomarkers in Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3201.
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Approaches for imaging disease biomarkers in the retina are needed to improve early detection, monitoring of disease progression, and assessment of therapeutic response. The goal of this study was to evaluate a new approach for in vivo imaging of messenger RNA (mRNA) and microRNA (miRNA) biomarkers in choroidal neovascularization.
Fluorescent dye-linked hairpin nucleic acid-functionalized gold nanoparticles (hAuNP) were engineered for targeting disease-relevant mRNA and miRNA biomarkers via intracellular delivery and target-specific hybridization. Intravenously-injected hAuNP were evaluated in mouse models of laser-induced choroidal neovascularization as well as age-matched controls. hAuNP were detected using in vivo optical imaging and imaging of tissue sections by confocal microscopy to determine specificity and sensitivity. hAuNP stability, biodistribution, toxicity, and off-target effects were evaluated in tissue culture and animal models.
hAuNP facilitated imaging of mRNA and miRNA biomarkers within neovascular lesions throughout the time course of laser induced choroidal neovascularization, including the mRNA biomarkers ICAM-1, VCAM-1, VEGFR2, and HIF1 alpha, as well as CNV-relevant miRNA biomarkers from the miRNA 23~24~27 family. Nonspecific controls, including scrambled hAuNP nanoparticles, did not emit appreciable signal in the retina. As assessed by toll-like receptor activation assays, TUNEL assays, and ERG analysis, hAuNP did not cause adverse effects in mice.
Optical imaging of hAuNP is a promising approach for detection of RNA biomarkers in animal models of retinal vascular disease. Due to their biocompatibility and specificity, hAuNP can be used for elucidating disease mechanisms and mediators, and have potential for clinical translation of diagnostic strategies.
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