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.
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