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H. Xu, M. Chen, E. Muckersie, J. V. Forrester; Complement Activation Is Not Essential for Retinal Degeneration in Aged Ccl2 or Ccr2-Dificient Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4282.
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Compelling evidence suggests that complement activation and monocyte malfunction are both involved in the pathogenesis of age-related macular degeneration (AMD). It is unclear, however, whether they are both required for the development of AMD. The aim of this study is therefore to investigate whether complement activation contributes to retinal degenerative changes in mice with CCL2 or CCR2 deficiency, the monocyte malfunction-type animal model of AMD.
Degenerative retinal changes in the CCL2 knockout (KO), CCR2 KO and C56BL/6 (wild-type) mice of different ages were examined clinically and histologically. Cryosections of mouse eyes were stained for complement C3, its fragments C3b/C3c and C3d and observed by confocal microscopy. Other complement factors including factor H (CFH) and factor B (CFB) were also investigated at both mRNA and protein levels.
Retinal degenerative changes were observed in aged CCL2- and CCR2-deficient mice. Complement C3, its fragments C3b/C3c and C3d were detected at Bruch’s membrane in all mice. The expression of C3b/C3c and C3d at Bruch’s membrane increased with age, suggesting age-related complement activation at Bruch’s membrane. There was no difference in the expression of complement C3, its fragments C3b/C3c and C3d at Bruch’s membrane between wild-type C57BL/6 mice and mice deficient in CCL2 or CCR2. In addition, we also observed no differece in the expression of other complement factors including CFH and CFB between wild-type controls and AMD mice at any age.
Complement activation is involved in retinal aging in normal physiological conditions. Retinal degenerative changes in CCL2- or CCR2-deficient mice do not involve abnormal complement activation. Monocyte malfunction on its own is enough to cause AMD-like pathology in the aging mice.
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