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 Aug 1;26(R1):R51-R57.
doi: 10.1093/hmg/ddx181.

From compliment to insult: genetics of the complement system in physiology and disease in the human retina

Robert F Mullins  1   2 , Alasdair N Warwick  3 , Elliott H Sohn  1   2 , Andrew J Lotery  4
Affiliations
Review

From compliment to insult: genetics of the complement system in physiology and disease in the human retina

Robert F Mullins et al. Hum Mol Genet. .

Abstract

Age-related macular degeneration (AMD) is a major cause of visual impairment that affects the central retina. Genome wide association studies and candidate gene screens have identified members of the complement pathway as contributing to the risk of AMD. In this review, we discuss the complement system, its importance in retinal development and normal physiology, how its dysregulation may contribute to disease, and how it might be targeted to prevent damage to the aging choriocapillaris in AMD.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Simplified summary of complement activation pathways. Genes with described polymorphisms associated with AMD are indicated by asterisks. While there are numerous fluid phase and cell surface complement inhibitors, deposition of the membrane attack complex (MAC) on the choriocapillaris is a consequence of normal aging but is much more striking in AMD and in patients with the high risk CFH genotype.
Figure 2
Figure 2
Age-related macular degeneration. Top panel, fundus appearance of a 65-year-old patient with AMD. Note the presence of drusen and pigment abnormalities in the macula. Lower panel, localization of the membrane attack complex (green) to domains surrounding the human choriocapillaris in an eye with AMD. Choroidal endothelial cells are labeled with UEA-I lectin (red) and nuclei appear blue (DAPI). The retinal pigment epithelium autofluoresces yellow in the preparation.
See this image and copyright information in PMC

References

    1. Fuess L.E., Eisenlord M.E., Closek C.J., Tracy A.M., Mauntz R., Gignoux-Wolfsohn S., Moritsch M.M., Yoshioka R., Burge C.A., Harvell C.D.. et al. (2015) Up in arms: immune and nervous system response to sea star wasting disease. PLoS ONE, 10, e0133053. - PMC - PubMed
    1. Gross P.S., Al-Sharif W.Z., Clow L.A., Smith L.C. (1999) Echinoderm immunity and the evolution of the complement system. Dev. Comp. Immunol., 23, 429–442. - PubMed
    1. Diebolder C.A., Beurskens F.J., de Jong R.N., Koning R.I., Strumane K., Lindorfer M.A., Voorhorst M., Ugurlar D., Rosati S., Heck A.J.R.. et al. (2014) Complement is activated by IgG hexamers assembled at the cell surface. Science, 343, 1260–1263. - PMC - PubMed
    1. Nepomuceno R.R., Henschen-Edman A.H., Burgess W.H., Tenner A.J. (1997) cDNA cloning and primary structure analysis of C1qR(P), the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro. Immunity, 6, 119–129. - PubMed
    1. Thurman J.M., Holers V.M. (2006) The central role of the alternative complement pathway in human disease. J. Immunol., 176, 1305–1310. - PubMed

Publication types

MeSH terms

Substances