Ranibizumab

The pathogenesis of neovascular eye diseases is not fully understood; however, vascular endothelial growth factor-A (VEGF-A) has been implicated in the development of clinical manifestations, such as choroidal neovascularization. Neovascularization is characterized by aberrated proliferation of abnormal vessels in the choroid capillary matrix. As a member of the VEGF family, VEGF-A is a key regulator of vascular permeability and angiogenesis; thus, it has been studied as a therapeutic target for the treatment of a wide array of neovascular eye diseases, including neovascular (wet) age-related macular degeneration (AMD) and diabetic retinopathy. For example, increased VEGF-A levels in the vitreous were shown in patients with neovascular age-related macular degeneration.

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody directed against human VEGF-A. Ranibizumab binds to VEGF-A with high affinity as well as its biologically active forms, such as VEGF165, VEGF121, and VEGF110. Notably, VEGF165 is the most predominant isoform in the human eye that promotes ocular neovascularization. VEGF165 enhances vascular permeability, inhibits apoptosis, and causes endothelial-cell mobilization from the bone marrow and differentiation for angiogenesis. Ranibizumab binds to the receptor-binding site of VEGF-A, preventing it from binding to its receptors - VEGFR1 and VEGFR2 - that are expressed on the surface of endothelial cells. Ranibizumab thereby attenuates endothelial cell proliferation, vascular leakage, and new blood vessel formation.