Complement factor H in AMD: Bridging genetic associations and pathobiology.

Journal Article (Journal Article;Review)

Age-Related Macular Degeneration (AMD) is a complex multifactorial disease characterized in its early stages by lipoprotein accumulations in Bruch's Membrane (BrM), seen on fundoscopic exam as drusen, and in its late forms by neovascularization ("wet") or geographic atrophy of the Retinal Pigmented Epithelial (RPE) cell layer ("dry"). Genetic studies have strongly supported a relationship between the alternative complement cascade, in particular the common H402 variant in Complement Factor H (CFH) and development of AMD. However, the functional significance of the CFH Y402H polymorphism remains elusive. In this article, we critically review the literature surrounding the functional significance of this polymorphism. Furthermore, based on our group's studies we propose a model in which CFH H402 affects CFH binding to heparan sulfate proteoglycans leading to accelerated lipoprotein accumulation in BrM and drusen progression. We also review the literature on the role of other complement components in AMD pathobiologies, including C3a, C5a and the membrane attack complex (MAC), and on transgenic mouse models developed to interrogate in vivo the effects of the CFH Y402H polymorphism.

Full Text

Duke Authors

Cited Authors

  • Toomey, CB; Johnson, LV; Bowes Rickman, C

Published Date

  • January 2018

Published In

Volume / Issue

  • 62 /

Start / End Page

  • 38 - 57

PubMed ID

  • 28928087

Pubmed Central ID

  • PMC5776047

Electronic International Standard Serial Number (EISSN)

  • 1873-1635

Digital Object Identifier (DOI)

  • 10.1016/j.preteyeres.2017.09.001


  • eng

Conference Location

  • England