Macrophages were previously implicated in the pathogenesis of neovascular age-related macular degeneration (nvAMD). It is unclear if a specific macrophage phenotype is associated with nvAMD, and if macrophages from nvAMD patients are more pathogenic as compared with controls. To address these issues, we evaluated macrophages derived from peripheral blood monocytes of nvAMD patients and age-matched controls. Macrophages were assessed in terms of their expression profile and of their angiogenic potential in the choroid sprouting assay and the rat model of laser-induced choroidal neovascularization. Results showed a proangiogenic and inflammatory gene and protein expression profiles in classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) polarized macrophages. Furthermore, activated macrophages, particularly of the M(IFNγ and LPS) phenotype from nvAMD patients, were proangiogenic ex vivo and in vivo. These findings implicate activated human macrophages, particularly M(IFNγ and LPS) macrophages from nvAMD patients, in nvAMD. Further research is required to determine whether activated macrophages can serve as therapeutic targets in nvAMD.
Keywords: Age-related macular degeneration; Angiogenesis; Choroidal neovascularization; Macrophages; Monocytes; Neuroinflammation.
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