AGING AND VASCULOGENESIS IN MACULAR DEGENERATION

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DESCRIPTION (provided by applicant): Age-related macular degeneration (ARMD) is the most important cause of vision loss in elderly patients. The major cause of severe vision loss in ARMD is pathologic neovascularization under the retina producing a lesion called choroidal neovascularization (CNV). The pathogenesis of the neovascular stage of ARMD is clearly multifactorial, but in general, is considered to be driven by angiogenesis, a process in which the cellular components of the new vessel complex (endothelial cells, smooth muscle cells and other types) are derived from cells resident within an adjacent pre-existing capillary. Recently an alternative paradigm, termed "postnatal vasculogenesis", has been shown to contribute to some forms of neovascularization. In vasculogenesis, the cellular components of the new vessel complex are derived, in part, from bone-marrow derived circulating vascular progenitors which differentiate into mature endothelial cells (EC) or vascular smooth muscle cells (VSMC) in situ. We propose that a significant proportion of EC and VSMC within CNV are derived from circulating vascular progenitors. We will use a combination of bone marrow transplantation, adoptive transfer and depletion techniques to evaluate the role of CD34 vascular progenitors in CNV formation, and how their function changes with aging.