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Stephanie Joachim, Christine Mondon, Sandra Kuehn, Sabrina Reinehr, Franz Grus, Burkhard Dick; Apoptotic retinal ganglion cell death in an autoimmune glaucoma model is accompanied by antibody depositions. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6110.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is characterized by death of retinal ganglion cells (RGCs), but its cause is still unknown. Our studies indicate that immunization with ocular antigens leads to RGC loss in a model of Experimental Autoimmune Glaucoma. To gain further knowledge about the mechanism and time-course of RGC cell death caspase 3 levels and possible antibody appearances were evaluated in this model.
Lewis rats were immunized with a optic nerve homogenate in Freund’s adjuvant and pertussis toxin (ONA), while the control group was injected with sodium chloride (CO). RGC density was quantified via retinal whole mounts and caspase 3+ cells were evaluated on retina cross-sections at 8, 12, and 22 days. IgM and IgG antibody deposits and GFAP reactivity were detected at the same points in time.
We detected no difference in caspase 3+ cells 8 days after immunization (p=0.23). At 14 days distinct IgM deposits were observed epiretinally in ONA animals and these animals had higher caspase 3+ rates (2.0±0.3) than controls (0.4±0.2; p=0.004). But both groups showed no difference in RGC density (p=0.62) at this time. At 22 days we detected a significantly higher number of apoptotic RGCs in ONA animals (ONA: 2.0±0; CO: 0.4±0.2; p=0.0007) and concurrent a lower RGC density (p=0.04). Regarding Ig deposits, 14 and 22 days after immunization we observed Igs in the ganglion cell layer (GCL) of ONA retinas. Especially 22 days after immunization we noted the IgG deposits are often in close vicinity to caspase+ cells in the GCL. The GFAP+ area in ONA retinas continuously increased. Already at 8 days ONA animals had a significantly higher mean GFAP+ area (7.2±0.5%) than CO (5.0±0.8%; p=0.02). Similar differences were noted at 14 days (CO=6.3±0.5%; ONA=7.1±1.0%; p=0.04). We observed the largest percentage of GFAP+ area in the ONA group (8.5±0.7%) at 22 days (CO: 6.1±0.6%; p=0.02).
Our data suggest that immunization with ocular antigens leads to apoptotic RGC death. Antibody deposits are detectable in the retina when apoptosis occurs. Therefore, we conclude that antibodies are engaged in eliciting RGC apoptosis in this animal model.
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