March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Characterisation of the Effects of Ageing on the Cfh-/- Mouse Retina
Author Affiliations & Notes
  • Jennifer A. Williams
    Cell Biology, Institute of Ophthalmology, UCL, London, United Kingdom
  • E. Rebecca Longbottom
    Cell Biology, Institute of Ophthalmology, UCL, London, United Kingdom
  • John Greenwood
    Cell Biology, Institute of Ophthalmology, UCL, London, United Kingdom
  • Stephen E. Moss
    Cell Biology, Institute of Ophthalmology, UCL, London, United Kingdom
  • Footnotes
    Commercial Relationships  Jennifer A. Williams, None; E. Rebecca Longbottom, None; John Greenwood, None; Stephen E. Moss, None
  • Footnotes
    Support  Medical Research Council and Wellcome Trust
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1664. doi:https://doi.org/
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      Jennifer A. Williams, E. Rebecca Longbottom, John Greenwood, Stephen E. Moss; Characterisation of the Effects of Ageing on the Cfh-/- Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1664. doi: https://doi.org/.

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

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Abstract

Purpose: : Dysregulation of the complement system in the eye is a feature of age-related macular degeneration (AMD), the leading cause of visual impairment in the UK. Several mutations in complement genes have been shown to increase an individual’s susceptibility to AMD. The Y402H single nucleotide polymorphism in complement factor H (CFH) is present in over 50% of AMD patients. CFH is a secreted regulator of the alternative complement pathway and therefore key to controlling the inflammatory response. Previous work in our group has shown that CFH is required for normal visual function in 2 year mice. In this study we characterise the retinas of Cfh-/- mice at 7-8 weeks and 1 year to gain insight into the effects of Cfh deletion on retinal ageing.

Methods: : 7-8 week and 1 year old Cfh-/- mouse retinas and age-matched wild-type controls were processed for morphological and ultrastructural analysis. Fixed eyes were sectioned or whole-mounted for immunohistochemistry. Electroretinograms were performed on 1 year old Cfh-/- mice and age-matched wild-type controls.

Results: : Morphological analysis revealed a reduction in photoreceptor density in wild-type mice with age and a further reduction with age in Cfh-/- mice. Immunohistochemical analysis showed that loss of CFH led to early signs of retinal stress and re-distribution of complement regulators at 1 year. Analysis of visual function by ERG revealed a significant increase in time to peak of the scotopic a-wave in 1 year old Cfh-/- mice.

Conclusions: : The loss of CFH in mice does not have a significant impact on the retina at 7-8 weeks of age. However, by 1 year the retina displays early signs of stress and accelerated features of ageing. We show that the retina is able to compensate for the deficiency of CFH by enhancing other complement regulators. Overall, this study reveals the importance of CFH in maintaining retinal health and visual function with age.

Keywords: age-related macular degeneration • inflammation • retina 
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