Fcγ receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration

Investigative Ophthalmology & Visual Science
Salome MurinelloJessica L Teeling

Abstract

Several lines of evidence suggest the involvement of antibodies and immune complex inflammation in AMD, a blinding disease with a strong inflammatory component. To examine this further, we developed a novel experimental mouse model of retinal inflammation and evaluated whether inflammation associated with immune complex formation was present in eyes of AMD donors. A localized immune complex-mediated reaction was induced in the retina of wild-type (WT), Fc receptor γ chain-deficient (γ(-/-)), and C1q-deficient (C1q(-/-)) mice, and donor eyes were obtained after death from donors with early or wet AMD and from healthy control subjects. The presence of immune complexes, Fcγ receptors (FcγRs), and markers of macrophage/microglia activation was investigated by immunohistochemistry. In WT and C1q(-/-) mice, immune complex deposition in the retina led to a robust inflammatory response with activation of microglia, recruitment of myeloid cells, and increased expression of FcγRI through FcγRIV and major histocompatibility complex class II. This response was not observed in γ(-/-) mice lacking activating FcγRs. We found that early AMD was associated with deposition of IgG, C1q, and membrane attack complex in the choriocapillaris and with...Continue Reading

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Citations

Dec 9, 2014·Progress in Retinal and Eye Research·S Scott WhitmoreRobert F Mullins
May 13, 2015·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Edward ChaumSujoy Bhattacharya
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