The case for complement and inflammation in AMD: open questions.

The complement cascade has been identified as a key factor in the pathogenesis of age-related macular degeneration (AMD). As a result, pharmacological modulation of the complement cascade is being investigated as a therapeutic strategy for AMD. The genetic data point to a triggering of the complement cascade, which subsequently cannot be damped down. Despite promising genetic, preclinical and immunolabeling data, important questions remain to be answered regarding the role of complement in the pathogenesis of AMD. The involvement of the complement cascade in the vision threatening stages of AMD, e.g. geographic atrophy and choroidal neovascularization, remain unknown. Additionally, the optimal component(s) of the complement cascade to be targeted for modulation still need to be identified. Answering these and other questions will provide investigators with a clear framework with which to evaluate progress in the field and help guide the development of future clinical therapeutics.