March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Complement Factor H Deficiency Results in Decreased Neuroretinal Expression of CD59 in Aged Mice
Author Affiliations & Notes
  • Carsten Faber
    Eye Research Unit, ISIM, University of Copenhagen, Copenhagen, Denmark
  • Jennifer Williams
    Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom
  • Helene Juel
    Eye Research Unit, ISIM, University of Copenhagen, Copenhagen, Denmark
  • John Greenwood
    Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom
  • Mogens Holst Nissen
    Eye Research Unit, ISIM, University of Copenhagen, Copenhagen, Denmark
  • Stephen E. Moss
    Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  Carsten Faber, None; Jennifer Williams, None; Helene Juel, None; John Greenwood, None; Mogens Holst Nissen, None; Stephen E. Moss, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1645. doi:
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    • Get Citation

      Carsten Faber, Jennifer Williams, Helene Juel, John Greenwood, Mogens Holst Nissen, Stephen E. Moss; Complement Factor H Deficiency Results in Decreased Neuroretinal Expression of CD59 in Aged Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1645.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The complement system plays a key role in age-related macular degeneration (AMD). Several complement genes are expressed in retinal pigment epithelium (RPE) and complement split-products and regulators accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. To examine the role of CFH in the ocular complement regulatory system, we analysed the expression of complement genes in neuroretinas, RPE/choroid and livers of young and old WT and Cfh-/- mice.

Methods: : Neuroretinas, RPE/choroid and liver tissue were isolated from young (~50 days) and old (~500 days) WT and Cfh-/- C57Bl/6 mice. Ocular RNA from two eyes/animal, four animals/group, was analysed with whole-transcript microarrays. Differential gene expression was validated with qRT-PCR. Liver RNA was analysed with qRT-PCR.

Results: : In RPE/choroid complement genes associated with activation of both the classical and alternative pathway including C1q, C3 and Factor B were upregulated with age. This coincided with increased expression of the negative regulators Cfh and Cd59 in neuroretina adding to the marked neuroretinal expression of negative regulators. Lack of age-dependent neuroretinal upregulation of Cd59 represented the main difference between WT and Cfh-/- mice. Hepatic expression of Cd59 and C1q increased with age independently of genotype. Hepatic expression of C3 and Factor B was equal in all groups and expression of Cfh was equal in young and old WT animals.

Conclusions: : The age-related upregulation of substrates, activators and inhibitors of the complement system in the retina is abnormal in mice deficient in CFH. This could explain the visual function deficits and morphological changes in the Cfh-/- mouse retina with age. Further, these results suggest that neuroretinal expression of CD59 depends on normal functioning CFH, thus pointing towards deficient neuroretinal complement regulation as an early event in some forms of AMD.

Keywords: retinal pigment epithelium • retina • age-related macular degeneration 
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