AGING AND VASCULOGENESIS IN MACULAR DEGENERATION

描述（由申请人提供）：视网膜相关性黄斑变性（ARMD）是老年患者视力丧失的最重要原因。 ARMD中严重视力丧失的主要原因是视网膜下的病理性新生血管形成，其产生称为脉络膜新生血管形成（CNV）的病变。ARMD的新生血管阶段的发病机制显然是多因素的，但一般认为是由血管生成驱动的，在血管生成过程中，新血管复合体的细胞组分（内皮细胞、平滑肌细胞和其他类型）来源于邻近预先存在的毛细血管内的细胞。最近，另一种被称为“出生后血管发生”的范式已被证明有助于某些形式的新血管形成。在血管发生中，新血管复合体的细胞组分部分源自骨髓来源的循环血管祖细胞，其原位分化成成熟内皮细胞（EC）或血管平滑肌细胞（VSMC）。我们认为CNV中的EC和VSMC很大一部分来源于循环血管祖细胞。我们将使用骨髓移植，过继转移和耗竭技术的组合来评估CD34血管祖细胞在CNV形成中的作用，以及它们的功能如何随着衰老而变化。

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.