AGING AND VASCULOGENESIS IN MACULAR DEGENERATION

描述(申请人提供)：老年性黄斑变性(ARMD)是导致老年患者视力丧失的最重要原因。ARMD严重视力丧失的主要原因是视网膜下的病理性新生血管产生一种称为脉络膜新生血管(CNV)的病变。ARMD新生血管阶段的发病机制显然是多因素的，但总的来说，被认为是由血管生成驱动的，在这个过程中，新血管复合体的细胞成分(内皮细胞、平滑肌细胞和其他类型)来自邻近预先存在的毛细血管内的细胞。最近，另一种范式，称为“出生后血管生成”，已经被证明有助于某些形式的新生血管形成。在血管生成中，新血管复合体的细胞成分部分来源于骨髓来源的循环血管前体细胞，后者在原位分化为成熟的内皮细胞(EC)或血管平滑肌细胞(VSMC)。我们认为CNV内很大比例的EC和VSMC来源于循环中的血管前体细胞。我们将结合骨髓移植、过继转移和耗竭技术来评估CD34血管前体细胞在CNV形成中的作用，以及它们的功能如何随年龄变化。

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.