Home LiteratureArticle Details
PMID: 17921253 Published · ppublish English Journal Article

Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 42 ·2007-10-16 ·Pages 16651-6

Coffey PJ, Gias C, McDermott CJ, Lundh P, Pickering MC, Sethi C, Bird A, Fitzke FW, Maass A, Chen LL, Holder GE, Luthert PJ, Salt TE, Moss SE, Greenwood J

Abstract

Age-related macular degeneration is the most common form of legal blindness in westernized societies, and polymorphisms in the gene encoding complement factor H (CFH) are associated with susceptibility to age-related macular degeneration in more than half of affected individuals. To investigate the relationship between complement factor H (CFH) and retinal disease, we performed functional and anatomical analysis in 2-year-old CFH-deficient (cfh(-/-)) mice. cfh(-/-) animals exhibited significantly reduced visual acuity and rod response amplitudes on electroretinography compared with age-matched controls. Retinal imaging by confocal scanning laser ophthalmoscopy revealed an increase in autofluorescent subretinal deposits in the cfh(-/-) mice, whereas the fundus and vasculature appeared normal. Examination of tissue sections showed an accumulation of complement C3 in the neural retina of the cfh(-/-) mice, together with a decrease in electron-dense material, thinning of Bruch's membrane, changes in the cellular distribution of retinal pigment epithelial cell organelles, and disorganization of rod photoreceptor outer segments. Collectively, these data show that, in the absence of any specific exogenous challenge to the innate immune system, CFH is critically required for the long-term functional health of the retina.

MeSH Terms
Aging Animals Complement C3/analysis,metabolism Complement Factor H/deficiency,genetics Fluorescence Immunity, Innate Mice Mice, Mutant Strains Retina/abnormalities,chemistry,ultrastructure Retinal Rod Photoreceptor Cells/physiopathology Vision Disorders/genetics
Chemicals
Complement C3 Complement Factor H
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Coffey Peter J
Division of Cellular Therapy, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
Gias Carlos
McDermott Caroline J
Lundh Peter
Pickering Matthew C
Sethi Charanjit
Bird Alan
Fitzke Fred W
Maass Annelie
Chen Li Li
Holder Graham E
Luthert Philip J
Salt Thomas E
Moss Stephen E
Greenwood John
References (37)
37 references, click to expand
  1. Complement factor H variant increases the risk of age-related macular degeneration.
    Science. 2005 Apr 15;308(5720):419-21 PMID: 15761120
  2. Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration.
    Am J Hum Genet. 2005 Jul;77(1):149-53 PMID: 15895326
  3. Estimation of systemic complement C3 activity in age-related macular degeneration.
    Arch Ophthalmol. 2007 Apr;125(4):515-9 PMID: 17420372
  4. Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium.
    Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16182-7 PMID: 17060630
  5. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration.
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14682-7 PMID: 12391305
  6. Drusen complement components C3a and C5a promote choroidal neovascularization.
    Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2328-33 PMID: 16452172
  7. Complement. First of two parts.
    N Engl J Med. 2001 Apr 5;344(14):1058-66 PMID: 11287977
  8. Photoreceptor loss in age-related macular degeneration.
    Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1236-49 PMID: 8641827
  9. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.
    Nat Genet. 2006 Apr;38(4):458-62 PMID: 16518403
  10. Photopic and scotopic fine matrix mapping of retinal areas of increased fundus autofluorescence in patients with age-related maculopathy.
    Invest Ophthalmol Vis Sci. 2004 Feb;45(2):574-83 PMID: 14744901
  11. Glial remodeling and neural plasticity in human retinal detachment with proliferative vitreoretinopathy.
    Invest Ophthalmol Vis Sci. 2005 Jan;46(1):329-42 PMID: 15623793
  12. Neurite outgrowth from bipolar and horizontal cells after experimental retinal detachment.
    Invest Ophthalmol Vis Sci. 1998 Feb;39(2):424-34 PMID: 9478003
  13. Cone- and rod-mediated multifocal electroretinogram in early age-related maculopathy.
    Eye (Lond). 2005 Apr;19(4):431-41 PMID: 15286663
  14. Fundus changes in membranoproliferative glomerulonephritis type II. A fluorescein angiographic study of 23 patients.
    Graefes Arch Clin Exp Ophthalmol. 1991;229(5):406-10 PMID: 1937071
  15. Functional loss in age-related Bruch's membrane change with choroidal perfusion defect.
    Invest Ophthalmol Vis Sci. 1992 Feb;33(2):334-40 PMID: 1740363
  16. Fundus autofluorescence in age-related macular disease imaged with a laser scanning ophthalmoscope.
    Invest Ophthalmol Vis Sci. 1997 Feb;38(2):478-86 PMID: 9040481
  17. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.
    Nat Genet. 2006 Oct;38(10):1173-7 PMID: 16998489
  18. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.
    Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32 PMID: 15870199
  19. Complement factor H polymorphism in age-related macular degeneration.
    Science. 2005 Apr 15;308(5720):385-9 PMID: 15761122
  20. Impact of aging and age-related maculopathy on inactivation of the a-wave of the rod-mediated electroretinogram.
    Vision Res. 2006 Apr;46(8-9):1422-31 PMID: 16242751
  21. Structure-function analysis of rods and cones in juvenile, adult, and aged C57bl/6 and Balb/c mice.
    Vis Neurosci. 2003 Mar-Apr;20(2):211-20 PMID: 12916741
  22. Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration.
    Hum Mol Genet. 2006 Sep 15;15(18):2784-90 PMID: 16905558
  23. Complement C3 variant and the risk of age-related macular degeneration.
    N Engl J Med. 2007 Aug 9;357(6):553-61 PMID: 17634448
  24. Risk factors for age-related macular degeneration: Pooled findings from three continents.
    Ophthalmology. 2001 Apr;108(4):697-704 PMID: 11297486
  25. Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: a histopathological report.
    Br J Ophthalmol. 1989 Apr;73(4):297-302 PMID: 2713310
  26. Complement. Second of two parts.
    N Engl J Med. 2001 Apr 12;344(15):1140-4 PMID: 11297706
  27. His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form.
    J Biol Chem. 2006 Aug 25;281(34):24713-20 PMID: 16787919
  28. Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments.
    Exp Eye Res. 2007 Apr;84(4):635-45 PMID: 17292886
  29. Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H.
    Nat Genet. 2002 Aug;31(4):424-8 PMID: 12091909
  30. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration.
    Prog Retin Eye Res. 2001 Nov;20(6):705-32 PMID: 11587915
  31. Complement activation and inflammatory processes in Drusen formation and age related macular degeneration.
    Exp Eye Res. 2001 Dec;73(6):887-96 PMID: 11846519
  32. Developmental plasticity of mouse visual acuity.
    Eur J Neurosci. 2003 Jan;17(1):167-73 PMID: 12534981
  33. Complement factor H polymorphism and age-related macular degeneration.
    Science. 2005 Apr 15;308(5720):421-4 PMID: 15761121
  34. H deficiency in two brothers with atypical dense intramembranous deposit disease.
    Kidney Int. 1986 Dec;30(6):949-56 PMID: 2950269
  35. A role for local inflammation in the formation of drusen in the aging eye.
    Am J Ophthalmol. 2002 Sep;134(3):411-31 PMID: 12208254
  36. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease.
    FASEB J. 2000 May;14(7):835-46 PMID: 10783137
  37. Convolution in human rods: an ageing process.
    Br J Ophthalmol. 1979 Mar;63(3):181-7 PMID: 435430
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0705079104
Published
2007-10-16
Epub
2007-00-05
Pages
16651-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2034255
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0705079104 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2