IMMUNE RESPONSES IN MACULAR DEGENERATION

描述(申请人提供)：老年性黄斑变性(ARMD)是老年人视力受损的最重要原因，仅在美国就有1400万患者受到影响。ARMD主要表现为干性ARMD和新生血管性ARMD两种类型：干性ARMD表现为视网膜色素上皮下玻璃体和其他沉积；新生血管性ARMD表现为脉络膜新生血管(CNV)，从脉络膜毛细血管下方侵入异常新生血管。巨噬细胞是天然免疫的主要效应细胞，见于脉络膜毛细血管下厚层沉积区域和新生血管内。我们认为，这些巨噬细胞是血液来源的单核细胞，被招募到绒毛毛细血管，以应对沉积堆积。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修饰物，根据其先前存在的激活状态是有益的还是有害的。目前的建议将继续研究，以支持部分激活的巨噬细胞与ARMD进展相关的假说，特别是CNV，并根据与ARMD发病相关的各种介质的表达来完善部分激活的巨噬细胞的定义。一个新的焦点将是检验这一假设，即巨细胞病毒慢性感染是部分ARMD患者单核细胞部分激活的原因之一。

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.