IMMUNE RESPONSES IN MACULAR DEGENERATION

描述（由申请人提供）：年龄相关性黄斑变性（ARMD）是老年人视力损害的最重要原因，仅在美国就影响了1400万患者。ARMD表现为两种形式：干ARMD，其特征是在RPE下积聚矿砂和其他沉积物；新血管性ARMD以脉络膜新生血管（CNV）为特征，即来自下绒毛毛细血管的异常新生血管的侵袭。巨噬细胞是先天性免疫的主要效应细胞，在厚沉积物的绒毛膜下区和CNV内观察到。我们认为这些巨噬细胞是血液来源的单核细胞，在沉积积累的反应中被募集到绒毛膜毛细血管。尽管巨噬细胞在ARMD中的致病作用尚不清楚，但我们的长期目标是确定巨噬细胞是疾病反应调节剂，其有益或有害取决于其预先存在的激活状态。目前的提案将继续研究部分活化的巨噬细胞与ARMD进展相关的假设，特别是CNV，并从与ARMD发病相关的各种介质的表达方面完善部分活化的巨噬细胞的定义。一个新的重点将是验证单核细胞慢性感染巨细胞病毒是部分ARMD患者单核细胞部分活化的原因之一的假设。

DESCRIPTION (provided by applicant): Age-related macular degeneration (ARMD) is the most important cause of visual impairment in the elderly, affecting 14 million patients in the US alone. ARMD is manifested as two forms: dry ARMD, characterized by the accumulation of drusen and other deposits under the RPE; and neovascular ARMD, characterized by choroidal neovascularization (CNV), the invasion of abnormal new vessels from the subjacent choriocapillaris. Macrophages, major effector cells of innate immunity, are observed in the choriocapillaris underlying areas of thick deposits and within CNV. We propose that these macrophages are blood-derived monocytes recruited to the choriocapillaris in response to deposit accumulation. Although their pathogenic contribution in ARMD remains unknown, our long term goal is to establish that macrophages are disease response modifiers that are either beneficial or harmful depending upon their pre-existing activation state. The current proposal will continue studies to support the hypothesis that partially activated macrophages are associated with ARMD progression, especially CNV, and to refine the definition of partially activated macrophages in terms of expression of various mediators relevant to ARMD pathogenesis. A new focus will be to test the hypothesis that chronic infection of monocytes with cytomegalovirus is one cause for the development of partially-activated monocytes in some ARMD patients.