The Role of the Immune Response in Age-Related Macular Degeneration

Figure 1

Schematic diagram of complement factor H (CFH). The protein consists entirely of 20 repeating homologous units (complement control repeats or CCPs), each ~60 amino acids in length (like beads on a string). The N-terminal portion houses the regulatory domains (repeats 1–4). The surface-binding recognition motifs are located in repeats 6–8, 12–14 and 19 and 20. They are also known as anionic- or heparin-binding sites. Both Y402H in repeat 7, and a rare variant in repeat 20 [12], are associated with AMD; these regions mediate the binding of factor H to cellular debris such as drusen or damaged retinal cells/tissues. Atypical hemolytic uremic syndrome (aHUS) has been compared to AMD because multiple variants leading to haploinsufficiency of factor H allow for excessive complement activation in this thrombomicroangiopathy [13–15]. Specifically, about 60% of the mutations in aHUS occur in repeats 19 and 20, which decrease factor H’s ability to bind to damaged endothelium. DAA, decay accelerating activity; CA, cofactor activity; Hep, heparin binding; CRP, C-reactive protein. Modified from Richards et al. [13].