Anti-Vascular Endothelial Growth Factor Agents for Pediatric Retinal Diseases

Abstract

The growth of blood vessels within the eye is essential for normal ocular development and maintenance. During early fetal development, the retina lacks blood vessels and depends on the primary vitreous, or hyaloid system, for vascular support. Subsequent regression of this hyaloid system coincides with the development of the mature retinal vasculature, consisting of 2 stages, vasculogenesis and angiogenesis. Vasculogenesis is the de novo formation of blood vessels from the differentiation of endothelial precursor cells, whereas angiogenesis is the formation of new vessels from existing vasculature. Vasculogenesis and angiogenesis, whether physiologic or pathologic, are tightly regulated processes requiring the coordinated action of specific molecular mediators. Extensive clinical and basic science research spanning many decades has confirmed vascular endothelial growth factor (VEGF) to be a key mediator of angiogenesis in the fetus as well as angiogenesis and vascular permeability in a multitude of ocular diseases. VEGF is the main mediator of ocular neovascularization, and is a powerful vascular permeability factor; VEGF induces the formation of fenestrae and destroys tight junctions in capillary walls leading to exudation and hemorrhage. The VEGF family of growth factors includes several isoforms: VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor.