Local Vs. Systemic Mononuclear Phagocytes in Age-Related Macular Degeneration and Their Regulation by CCL2–CCR2 and CX3CL1–CX3CR1 Chemokine Signalling

Abstract

Mononuclear phagocytes are myeloid-derived effector cells of the innate immune system and comprise peripheral blood monocytes, dendritic cells, tissue macrophages and retinal and brain microglia. Mononuclear phagocytes have been previously implicated in the pathology of age-related macular degeneration (AMD), but it remains unclear, whether recruitment of mononuclear cells from the periphery to the choroid and retina as well as local microglia activation is secondary or primary events in AMD pathogenesis. The identification of functional polymorphisms in the chemokine receptor CX3CR1 with increased risk to develop AMD highlights the importance of chemokine signalling in AMD and supports the hypothesis that aberrant chemokine signalling might play a more primary role than so far anticipated. We here review the evidence for an involvement of myeloid cells in the pathology of AMD and discuss how two major chemotactic cytokine pathways, CCL2–CCR2 and CX3CL1–CX3CR1, control recruitment of systemic monocyte subsets to the retina, how they regulate local activation of macrophages/microglia in the eye and how defects in these signalling pathways might contribute to AMD pathology.