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Oliver Gramlich, Sabine Beck, Anika Ziegler, Norbert Pfeiffer, Franz Grus; Autoimmune component in glaucoma: IgG autoantibody accumulation, plasma cells and microglia under pro-inflammatory conditions. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3176.
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An autoimmune component is discussed in the pathology of glaucoma due to the alteration of autoantibodies in sera and aqueous humor, but less is known about the role of these autoantibodies. It is currently unknown whether IgG accumulates in the glaucomatous retina and which cellular components, e.g. B-cells and microglia, are involved or how the retinal homeostasis is affected in a pathogenetic way.
Globes of six human glaucomatous donor eyes and nine healthy samples were splitted and antibody microarrays were used to examine the patterns of pro-inflammatory proteins and microglial markers (iba1) in the dissected retina. Global normalization coefficients were applied and revealed a normalized intensity for each antibody reactivity. The other half globe was fixed in 4%PFA, paraffin-embedded and sliced in 10µm cross-sections. Beside a calculation of remaining cells in the retinal ganglion cell-layer and the proof of IgG occurrence, several Abs against CD3, CD20, CD27 and iba1 were used for immunohistochemistry to identify possibly involved cellular players. Data underwent student's t-test analysis.
Antibody microarray analysis revealed an increased level of pro-inflammatory components in the glaucomatous group like TNF-α (+68%), IL 1β (+38%), IL 6 (+45%) and IL 8 (+34%). Ratios of single complement components were altered, while the total amount of all complement proteins did not differ. In glaucoma tissues, a significantly reduced amount of remaining cells in the retinal ganglion cell-layer was found (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p=0.0007). Cell loss was accompanied by a twofold higher amount of retinal IgG accumulations (healthy: 5.0±0.5 IgG/100 cells, glaucoma: 9.4±1.9 IgG/100 cells; p=0.004), and likewise co-localized by microglia. Appropriately, iba1 levels were increased by +29% in glaucoma. Moreover, B-cells (1.8±1 100/cells), CD27+ cells and CD27+/IgG+ plasma cells were observed exclusively in glaucomatous retinas.
The study provides evidences for IgG deposition and occurrence of plasma cells in human glaucomatous retina. The result suggests that these IgG deposits occurred in a pro-inflammatory environment, which seems to be maintained locally by immune-competent cells like microglia. There are hints that ganglion cell death in glaucoma is partly mediated by antibody-dependent-cellular-cytotoxicity.
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