Figure 2.

Mechanism of action of anti-VEGF treatments currently used to treat neovascular age related macular edema. Activation of VEGFR2 by VEGF-A plays a major role during angiogenesis, the role of VEGFR1 and VEGFR3 during neovascularization is less pronounced. Binding of ANG2 to TIE2 and Integrin α5β1, αvβ5, α3β1 and αvβ3 will further. All the antiangiogenic agents used to treat age related macular degeneration, binding to VEGF-A and prevent its signaling. Aflibercept, which is a fusion protein, will also bind to PLGF and VEGF-B. Faricimab instead is a bi-specific antibody and will bind to both ANG2 and VEGF-A. Whether faricimab will inhibit binding of ANG2 to integrins is less well characterized than its capability to intervene with ANG2-TIE2 signaling. Both ranibizumab and brolucizumab antibody fragments that inhibit VEGF-A signaling. Brolucizumab is a humanized monoclonal single-chain Fv (scFv) antibody fragment and ranibizumab is a humanized monoclonal antibody fragment. VEGF-C and VEGF-D are ligands for both VEGFR-3 and VEGFR-2 and may mediate pro-angiogenic signals even in the presence of previously mentioned anti-VEGF treatments. Abbreviations: PLGF, placental growth factor; VEGF, vascular endothelial growth factor; ANG, angiopoietin; VEGFR, vascular endothelial growth factor receptor, TIE, tyrosine kinase with Ig and EGF homology domains.