Age-related macular degeneration (AMD) is the most prevalent cause of
blindness in the elderly, and its exsudative subtype critically depends on local production of
vascular endothelial growth factor A (
VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce
VEGF. Their precursors, for example monocytes, can be recruited to sites of
inflammation by the
chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular
VEGF content in a
laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the
VEGF content in cell subsets from the
laser-treated retina and choroid separately. 3 days after
laser, macrophage numbers and their
VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained
VEGF after
laser, and this was CCR2-independent. On day 6,
VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of
VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their
VEGF content was not increased after
laser. When we analyzed flatmounts of
laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after
laser. In summary, CCR2-dependent influx of macrophages causes a transient
VEGF increase in the choroid. However, macrophages augmented
choroidal neovascularization only initially, presumably because
VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of
VEGF in
laser-induced
choroidal neovascularization but suggest that the therapeutic efficacy of CCR2-inhibition might be limited.