Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Apr:84:65-76.
doi: 10.1016/j.molimm.2016.11.016. Epub 2016 Dec 6.

The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment

Maartje J Geerlings  1 , Eiko K de Jong  1 , Anneke I den Hollander  2
Affiliations
Review

The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment

Maartje J Geerlings et al. Mol Immunol. 2017 Apr.

Abstract

Age-related macular degeneration (AMD) is a progressive retinal disease and the major cause of irreversible vision loss in the elderly. Numerous studies have found both common and rare genetic variants in the complement pathway to play a role in the pathogenesis of AMD. In this review we provide an overview of rare variants identified in AMD patients, and summarize the functional consequences of rare genetic variation in complement genes on the complement system. Finally, we discuss the relevance of this work in light of ongoing clinical trials that study the effectiveness of complement inhibitors against AMD.

Keywords: Age-related macular degeneration; Alternative pathway; Complement system; Rare genetic variants.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Rare coding variants in CFH, CFI, C3 and C9 found in AMD patients. Variants are color-coded as follows: significantly (p < 0.05) associated with AMD in one or more AMD case-control cohorts (in red), were found in AMD families (in orange), were found in more than one AMD cohort (in green), or were found in one AMD cohort (in blue). Variants notated with ‡ have a functional effect on the protein or change systemic levels. CFH: Complement Factor H; CFI Complement Factor I; C3 Complement C3; C9 Complement C9.
See this image and copyright information in PMC

References

    1. AREDS Age Related Eye Disease Study Research Group, A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 2001;119:1417–1436. (Chicago, Ill.: 1960) - PMC - PubMed
    1. Abecasis G.R., Yashar B.M., Zhao Y., Ghiasvand N.M., Zareparsi S., Branham K.E., Reddick A.C., Trager E.H., Yoshida S., Bahling J., Filippova E., Elner S., Johnson M.W., Vine A.K., Sieving P.A., Jacobson S.G., Richards J.E., Swaroop A. Age-related macular degeneration: a high-resolution genome scan for susceptibility loci in a population enriched for late-stage disease. Am. J. Hum. Genet. 2004;74:482–494. - PMC - PubMed
    1. Albuquerque J.A., Lamers M.L., Castiblanco-Valencia M.M., Dos Santos M., Isaac L. Chemical chaperones curcumin and 4-phenylbutyric acid improve secretion of mutant factor H R127H by fibroblasts from a factor H-deficient patient. J. Immunol. 2012;189:3242–3248. (Baltimore, Md.: 1950) - PubMed
    1. Alexander P., Gibson J., Cree A.J., Ennis S., Lotery A.J. Complement factor I and age-related macular degeneration. Mol. Vis. 2014;20:1253–1257. - PMC - PubMed
    1. Bienaime F., Dragon-Durey M.A., Regnier C.H., Nilsson S.C., Kwan W.H., Blouin J., Jablonski M., Renault N., Rameix-Welti M.A., Loirat C., Sautes-Fridman C., Villoutreix B.O., Blom A.M., Fremeaux-Bacchi V. Mutations in components of complement influence the outcome of factor I-associated atypical hemolytic uremic syndrome. Kidney Int. 2010;77:339–349. - PubMed

Publication types

Substances