Quantum Dot-Based Profile Imaging of EPC Subpopulations and Effect on Retinal NV

Vanderbilt University, Nashville TN

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Abstract

DESCRIPTION (provided by applicant): Endothelial progenitor cells (EPCs) are highly significant participants in the neovascular component of a host of diseases, such as atherosclerosis and cancer. Current research on endothelial progenitor cells has identified several different subpopulations expressing varying phenotypes according to the subset of antigens that are expressed on the cells'surface. Furthermore, evidence is suggestive of varying functions among progenitor cell subpopulations in disease. Specifically, the recruitment of EPCs to sites of neovascularization may be a subpopulation-specific phenomenon. Thus, an elucidation of EPC function based on antigenically-defined subpopulations may facilitate the development of customized, high-efficacy therapeutics aimed at the inhibition or enhancement of EPC function, as well as a more detailed understanding of the role of EPCs in the pathogenesis of numerous diseases. Current in vivo imaging tools to profile the activities of multiple cell subtypes in the circulation have not been developed. We seek to assess the neovascular capacity of various endothelial progenitor subsets using an established animal model of retinopathy of prematurity, in conjunction with a real-time, multispectral, quantum dot nanocrystalbased imaging system which enables a continuous, non-invasive view of the retinal circulation. Our effort is an outgrowth of the Penn laboratory's expertise in the pathogenesis and development of therapeutic interventions of retinopathy of prematurity, as well as the recent effort to isolate and culture distinct EPC subsets. The Haselton laboratory has recently developed a multispectral, real-time imaging tool for the study of multiple cellular and biomolecular mediators of inflammation in a rat model of diabetes. Our approach will use the quantum dot coding of cell subpopulations with varying molecular expression profiles to probe EPC activity in the retinal circulation, thus affording, for the first time, a high-throughput template for the elucidation of EPC function in the context of cell subtypes, as well as the evaluation of therapeutic interventions directed towards these subtypes, in real-time at high spatial and temporal resolution.