Figure 4.

Cascade of events in the angiogenic process. Photoreceptors and retinal pigment epithelium (RPE) produce vascular endothelial growth factor (VEGF), which stimulates monocytes through monocyte colonization protein (MCP) and interleukin-8 (IL-8). Macrophage activation increases the levels of tumor necrosis factor α (TNF-α), increasing the levels of IL-8, MCP, and VEGF. These mediators stimulate endothelial cell (EC) migration from choriocapillaris (CC) and proliferation, leading to new vessel formation (angiogenesis). The newly formed neovascular tissue grows under the balance between matrix metalloproteinases (MMPs), produced by endothelial cells and macrophages, and tissue inhibitors of metalloproteinases (TIMPs), produced by RPE. Vascular remodeling and the subsequent stabilization of the neovascular membrane is favored by the equilibrium of several mediators, including angiopoietins, acidic and basic fibroblast growth factor (aFGF and bFGF), and transforming growth factor beta (TGFβ).