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Salome Murinello, Andrew J. Lotery, V. Hugh Perry, Jessica L. Teeling; The Inflammatory Response To Immune Complex Formation In The Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6475.
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A growing body of evidence suggests that immunologic events play a crucial role in the pathogenesis of age-related macular degeneration (AMD). The presence of anti-retinal antibodies, complement and activated macrophages/microglia in drusen implicates immune complex mediated inflammation in the disease. Immune complex responses in the eye have been poorly characterised. We believe understanding the dynamics of immune complex formation in the retina and their interaction with Fcγ receptor (FcγR) expressing macrophages/microglia may delineate the mechanisms underlying drusen formation and the development of pathology in AMD. In this study, we used the reverse Arthus reaction to induce immune complexes in the murine retina and study their effects on retinal inflammation and integrity.
Balb/C mice were immunized against ovalbumin (OVA), followed by an intravitreal challenge of OVA or saline. Tissue was collected at various time points following OVA challenge and analysed for the presence of IgG, C3, microglial activation and neovascularisation by immunohistochemistry using both retinal sections and whole-mounts. Cytokine and growth factor production was analysed by qPCR.
Immune complexes formed throughout the retina, including large deposits in the subretinal space (Figure 1). These deposits were associated with changes to the retinal immune system, including altered morphology of microglia and their migration towards immune complexes, recruitment of macrophages from the circulation and increased GFAP expression. In addition, a change to microglial function was also evident as expression of MHCII, CD11b, CD68 and CD16/32 was increased and pro-inflammatory were cytokines elevated.
These results suggest that immune complexes formed in the retina induce a potent inflammatory response with up-regulation of FcγRs on microglia and macrophages and increased mRNA expression of pro-inflammatory cytokines. This may be of relevance for retinal diseases such as AMD where immune complexes form and could provide a possible mechanism by which microglia/macrophage changes could contribute to the pathology of the disease.
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