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Prog Retin Eye Res. 2018 Jan;62:38-57. doi: 10.1016/j.preteyeres.2017.09.001. Epub 2017 Sep 18.

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

Author information

1
Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University, Durham, NC 27710, USA.
2
Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
3
Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University, Durham, NC 27710, USA. Electronic address: bowes007@duke.edu.

Abstract

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.

PMID:
28928087
PMCID:
PMC5776047
DOI:
10.1016/j.preteyeres.2017.09.001
[Indexed for MEDLINE]
Free PMC Article

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