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Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.

ABSTRACT: 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.

SUBMITTER: Faber C

PROVIDER: S-EPMC3465015 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.

Faber Carsten C Williams Jennifer J Juel Helene Bæk HB Greenwood John J Nissen Mogens Holst MH Moss Stephen E SE

Investigative ophthalmology & visual science 20120919 10

<h4>Purpose</h4>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.<h4>Methods</h4>Gene ...[more]

PMID: 22918646

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Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.

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Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice.

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