STRATEGIES FOR INHIBITING AGE-RELATED MACULAR DEGENERATION

Vascular endothelial growth factor (VEGF), a potent mediator of new blood vessel growth, encompasses multiple receptors and ligands. Expression of both the receptors and the ligands differs across tissues and cell types. The initial inhibitors of VEGF were targeted at one of its several receptors, but subsequent inhibitors of intracellular components of VEGF and downstream enzymatic signaling have also been associated with potent antiangiogenic effects. In cancer, single-agent inhibitors of VEGF have been associated with modest clinical benefits against many types of malignancy. Although greater cancer control is typically achieved when VEGF pathway inhibitors are combined with conventional cytotoxic agents, it is possible that blocking multiple signaling pathways or multiple steps along a single pathway will yield greater therapeutic effects. Encouraging preliminary results with antiangiogenic combinations may be relevant to both cancer and other pathogenic states, such as age-related macular degeneration, where antiangiogenic agents are active. RETINA 29:S21-S23, 2009