| First Author | Murinello S | Year | 2014 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 55 |
| Issue | 1 | Pages | 247-58 |
| PubMed ID | 24334446 | Mgi Jnum | J:229147 |
| Mgi Id | MGI:5750855 | Doi | 10.1167/iovs.13-11821 |
| Citation | Murinello S, et al. (2014) Fcgamma receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration. Invest Ophthalmol Vis Sci 55(1):247-58 |
| abstractText | PURPOSE: 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. METHODS: A localized immune complex-mediated reaction was induced in the retina of wild-type (WT), Fc receptor gamma chain-deficient (gamma(-/-)), 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, Fcgamma receptors (FcgammaRs), and markers of macrophage/microglia activation was investigated by immunohistochemistry. RESULTS: 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 FcgammaRI through FcgammaRIV and major histocompatibility complex class II. This response was not observed in gamma(-/-) mice lacking activating FcgammaRs. 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 FcgammaRIIa and FcgammaRIIb. Furthermore, FcgammaRIIa and FcgammaRIIb were observed in eyes of donors with wet AMD. CONCLUSIONS: Our studies suggest that immune complexes may contribute to AMD pathogenesis through interaction of IgG with FcgammaRs and might inform about possible adverse effects associated with therapeutic antibodies. |
