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Salome Murinello, Robert F. Mullins, Andrew J. Lotery, V. Hugh Perry, Jessica L. Teeling; Fcγ Receptor Upregulation Is Associated With Immune Complex Inflammation in the Mouse Retina and Early Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(1):247-258. doi: https://doi.org/10.1167/iovs.13-11821.
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© ARVO (1962-2015); The Authors (2016-present)
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 increased numbers of CD45+ cells expressing FcγRIIa and FcγRIIb. Furthermore, FcγRIIa and FcγRIIb were observed in eyes of donors with wet AMD.
Our studies suggest that immune complexes may contribute to AMD pathogenesis through interaction of IgG with FcγRs and might inform about possible adverse effects associated with therapeutic antibodies.
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