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Ashwath Jayagopal, Andrew Y. Gordon, Megan E. Capozzi; Molecular Imaging of mRNA in Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2996. doi: https://doi.org/.
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Early detection of disease biomarkers in the retina in vivo would facilitate earlier detection of disease and enhance effectiveness of therapy. However, the development of protein-targeted agents for this purpose has been limited. The goal of this study was to evaluate a new approach for in vivo imaging of mRNA biomarkers in living ocular tissue for the purpose of detecting neovascular AMD-associated biomarkers.
Infared dye-linked hairpin DNA-functionalized gold nanoparticles (hAuNP) were engineered for targeting disease-relevant mRNA biomarkers including HIF1 alpha, VCAM-1, and VEGFR2, as well as housekeeping transcripts such as beta actin. Nanoparticles were evaluated in a mouse model of laser-induced choroidal neovascularization as well as age-matched controls. hAuNP were injected systemically or intraocularly, and imaged using optical imaging in vivo and ex vivo in animal models to evaluate specificity and sensitivity.
hAuNP facilitated imaging of neovascular AMD biomarkers within neovascular lesions throughout the timecourse of laser induced choroidal neovascularization, with signal to noise ratios exceeding 10:1. Nonspecific controls, including scrambled hairpin DNA-functionalized nanoparticles, did not emit appreciable signal in the retina. hAuNP administered by either injection route were capable of binding to target mRNA within lesions. hAuNP were capable of simultaenous imaging of multiple mRNA biomarkers within the same animal retina in vivo.
hAuNP are promising nanoscale optical agents for imaging mRNA biomarkers in ocular diseases such as neovascular AMD. This imaging approach will facilitate construction of molecularly-targeted contrast agents capable of imaging virtually any disease biomarker in neovascular disease, due to the ease of design and synthesis and homing capability.
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