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
. 2018 Nov;32(11):1740-1742.
doi: 10.1038/s41433-018-0170-8. Epub 2018 Jul 16.

Evaluation of serum and ocular levels of membrane attack complex and C-reactive protein in CFH-genotyped human donors

Affiliations

Evaluation of serum and ocular levels of membrane attack complex and C-reactive protein in CFH-genotyped human donors

Kathleen R Chirco et al. Eye (Lond). 2018 Nov.

Abstract

Background: There is a considerable body of evidence demonstrating a link between the membrane attack complex (MAC) and age-related macular degeneration (AMD), and between C-reactive protein (CRP) and AMD. Both the MAC and the monomeric form of CRP (mCRP) accumulate within the choriocapillaris in AMD. However, the precise contribution of these species to AMD pathophysiology has not been fully elucidated.

Methods: We sought to directly assess CRP and MAC levels between human serum and ocular tissues from the same CFH Y402H genotyped donors using ELISA of serum and RPE/choroid proteins.

Results: The Y402H polymorphism was associated with significantly increased MAC in RPE/choroid samples, but not in the serum, in a previously unstudied cohort. While MAC levels in the choroid were independent of circulating levels, choroidal CRP was correlated to serum levels.

Conclusions: These data provide further evidence for local activation of complement within the choriocapillaris in AMD.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
CRP (ac) and sC5b-9/MAC (df) levels in the RPE/choroid and serum of genotyped human donors. Box-and-whisker plots, showing median, interquartile range, and minimum and maximum values, for RPE/choroid tissue (a, d) and serum (b, e) for low-risk (YY) and high-risk (HH) CFH donors. Direct comparisons between serum and tissue protein levels reveal a regression line with a significantly non-zero slope for CRP (R2 = 0.3543; c) but not for MAC (R2 = 0.0377; f). *p < 0.05

References

    1. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308:385–9. doi: 10.1126/science.1109557. - DOI - PMC - PubMed
    1. Whitmore SS, Sohn EH, Chirco KR, Drack AV, Stone EM, Tucker BA, et al. Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy. Prog Retin Eye Res. 2015;45:1–29. doi: 10.1016/j.preteyeres.2014.11.005. - DOI - PMC - PubMed
    1. Chirco KR, Whitmore SS, Wang K, Potempa LA, Halder JA, Stone EM, et al. Monomeric C‐reactive protein and inflammation in age‐related macular degeneration. J Pathol. 2016;240:173–83. doi: 10.1002/path.4766. - DOI - PMC - PubMed
    1. Bhutto IA, Baba T, Merges C, Juriasinghani V, McLeod DS, Lutty GA. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration. Br J Ophthalmol. 2011;95:1323–30. doi: 10.1136/bjo.2010.199216. - DOI - PMC - PubMed
    1. Johnson PT, Betts KE, Radeke MJ, Hageman GS, Anderson DH, Johnson LV. Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid. Proc Natl Acad Sci USA. 2006;103:17456–61. doi: 10.1073/pnas.0606234103. - DOI - PMC - PubMed