Age-related macular degeneration (AMD) is the leading cause of blindness in the USA. Polymorphisms in various complement components are associated with an increased risk for AMD, and it has been hypothesized that an overactive complement system is partially responsible for the pathology of AMD. AMD is classified as early, intermediate, or late AMD, depending on the degree of the associated pathologies. Late AMD can be characterized as either lesions associated with neovascular AMD or geographic atrophy. Both sets of lesions are associated with pathology at the RPE/choroid interface, which include a thickening of Bruch's membrane, presence of drusen, and pigmentary alterations, and deterioration of the blood-retina barrier has been reported. These changes can lead to the slow degeneration and atrophy of the photoreceptors in the macula in dry AMD, or progress to choroidal neovascularization (CNV) and leakage of these new vessels in wet AMD. It has been shown previously that complement anaphylatoxins C3a and C5a, signaling via their respective G-protein-coupled receptors, can alter RPE cell function and promote choroidal neovascularization. However, it is important to note these components also play a role in tissue repair. Here we discuss anaphylatoxin signaling in AMD-related target cells and the potential implications for the design of anti-complement therapeutics.
