Related Experiment Video
Updated: May 19, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice
Carsten Faber1, Jennifer Williams, Helene Bæk Juel
1University of Copenhagen, Faculty of Health Sciences, ISIM, Copenhagen, Denmark. carstenfaber@gmail.com
Insights
Complement factor H (CFH) deficiency in mice impairs age-related upregulation of CD59 in the retina, suggesting tissue-specific regulation critical for preventing age-related vision changes.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- The complement system plays a key role in age-related macular degeneration (AMD) pathogenesis.
- Complement factor H (CFH) variants are linked to AMD risk, but its precise role in ocular disease is unclear.
- Ocular complement gene expression and protein accumulation occur in AMD.
Purpose of the Study:
- To investigate the impact of aging and CFH deficiency on ocular complement gene expression in mice.
- To compare ocular complement expression patterns with those in the liver.
Main Methods:
- Gene expression analysis using microarrays in neuroretinas and RPE/choroid of young and aged wild-type (WT) and CFH null mutant mice.
- Comparison of ocular gene expression with hepatic expression.
Main Results:
- Age-associated increase in complement genes (C1q, C3, factor B) in RPE/choroid of WT mice.
- Age-associated increase in negative regulators CFH and CD59a in the neuroretina of WT mice.
- CFH-deficient mice failed to upregulate neuroretinal CD59a with age, unlike WT mice, while hepatic CD59a expression increased with age regardless of CFH status.
Conclusions:
- Neuroretinal CD59a regulation is dependent on CFH, indicating tissue-specific effects.
- CFH deficiency may contribute to age-related visual deficits and retinal changes observed in Cfh(-/-) mice.
- The findings suggest a potential mechanism linking CFH dysfunction to AMD pathogenesis.
Purpose:
The complement system is closely linked to the pathogenesis of AMD. Several complement genes are expressed in RPE, and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice.
Methods:
Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh(-/-) C57BL/6J mice was analyzed by microarrays. Expression of a wide range of complement genes was compared with expression in liver.
Results:
An age-associated increased expression of complement, particularly C1q, C3, and factor B, in the RPE/choroid coincided with increased expression of the negative regulators Cfh and Cd59a in the neuroretina. Young mice deficient in CFH expressed Cd59a similar to WT, but failed to upregulate Cd59a expression with age. Hepatic expression of Cd59a increased with age regardless of Cfh genotype.
Conclusions:
While the connection between CFH deficiency and failure to upregulate CD59a remains unknown, these results suggest that expression of CD59 is tissue-specific and that neuroretinal regulation depends on CFH. This could contribute to the visual functional deficits and morphological changes in the Cfh(-/-) mouse retina that occur with age.
