, 2011), although they do not predict disease progression

once advanced AMD has developed (Klein et al., 2010 and Scholl et al., 2009). Also, since there are no approved treatments for GA, any analysis of factors that increase GA risk or progression, including information gleaned from AMD biomarkers (Gu et al., 2009 and Guymer et al., 2011), provides therapeutically inactionable information at present. Variation in multiple complement system genes (Bird, 2010 and Bradley et al., 2011) is one of the most consistent statistical associations with AMD risk. It bears noting that the discovery of complement dysregulation in AMD based on biochemical approaches (Baudouin et al., 1992, Hageman et al., 2001 and Johnson et al., 2001) predated the identification of sequence variations in complement genes (Edwards et al., 2005, Hageman et al., 2005, Haines et al., 2005 and Klein et al., 2005). The complement gene variant conferring the this website greatest quantitative statistical AMD risk is factor H (CFH). CFH inhibits a key activation step in complement activation, thereby reducing complement-induced host cell damage and inflammation. Still, there exists a very low sensitivity

and specificity in terms of using genetic variation in CFH alone to determine AMD risk. In fact, when taking into consideration disease prevalence, the positive predictive value of genetic variation to assess learn more AMD risk is anemic, even when multiple genetic

loci are considered ( Jakobsdottir et al., 2009). Nevertheless, the predictive power of AMD risk assessment can be augmented greatly by considering genetic information from multiple loci in combination with epidemiologic and environmental risk factors. Indeed, many nongenetic, environmental risk factors for AMD have been identified, and for further discussion on this topic the reader is directed to excellent and comprehensive reviews (Ambati et al., 2003a, Chakravarthy et al., 2010 and Krishnadev et al., 2010). In addition, onset and affection status of the fellow eye can be strongly influenced by an aggregated genetic risk (Chen et al., 2011). Next-generation sequencing technologies combined with rigorous biological definition of mechanistic implications of the identified variants are likely to yield more valuable insights both into disease pathogenesis Urease and rational development of novel diagnostics and therapeutics in the coming decade. Here, we will review the frontline experimental approaches and potential future directions for the treatment of AMD. We will also discuss the mechanistic justification of these interventions. Complement inhibition as a therapeutic strategy represents the culmination of numerous research articles that focus on the role of complement in AMD pathogenesis. Although complement inhibition suppresses CNV in animal models of wet AMD, it has not been shown to ameliorate dry AMD in vivo.