Vascular endothelial growth factor and the eye: biochemical mechanisms of action and implications for novel therapies

Ophthalmic complications arising from pathologic intraocular neovascularization are responsible for the majority of visual loss in most developed countries. Among the many disorders associated with intraocular neovascularization are retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. These conditions are the leading causes of blindness among infants, those of working age and the elderly, respectively. For nearly half a century the clinical findings associated with these conditions have suggested that the action of growth factors may play a pivotal role in the pathogenesis of these diseases. However, the exact molecules involved and their mechanisms of action have remained incompletely understood. Recently, studies have begun to elucidate the major molecules and intracellular pathways involved in regulating neovascular eye disorders. Vascular endothelial growth factor has been implicated as a major mediator of intraocular neovascularization and permeability. The recent insights into the mechanisms of intraocular angiogenesis have provided new targets for novel nondestructive therapeutic agents directed toward preventing the visual loss associated with ophthalmic neovascular disorders.