AGING AND VASCULOGENESIS IN MACULAR DEGENERATION

黄斑变性中的衰老和血管生成

基本信息

批准号：
6719966
负责人：
SCOTT W COUSINS
金额：
$ 15.15万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2007-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6719966
关键词：
CD43 molecule age difference angiogenesis animal old age bone marrow transplantation cell cycle cell differentiation cell population study disease /disorder model genetic regulation green fluorescent proteins immature animal laboratory mouse macular degeneration retina circulation stem cells vascular endothelium vascular smooth muscle

项目摘要

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.

描述（由申请人提供）：与年龄相关的黄斑变性（ARMD）是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新血管形成，产生称为脉络膜新生血管形成（CNV）的病变。 ARMD的新血管阶段的发病机理显然是多因素的，但通常被认为是由血管生成驱动的，在这种过程中，新容器复合物的细胞成分（内皮细胞，平滑肌细胞和其他类型）的过程是由血管生成驱动的。细胞居住在相邻的先前毛细管中。最近，一种被称为“产后血管生成”的替代范式已被证明会导致某些形式的新血管形成。在血管生成中，新血管复合物的细胞成分部分是从骨髓衍生的循环血管祖细胞中得出的，这些血管祖细胞分化为成熟的内皮细胞（EC）或血管平滑肌细胞（VSMC）。我们建议，CNV内的EC和VSMC很大一部分来自循环的血管祖细胞。我们将使用骨髓移植，产卵和耗尽技术的结合来评估CD34血管祖细胞在CNV形成中的作用，以及它们的功能如何随老化而变化。