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Stephanie C. Joachim, Oliver W. Gramlich, Burkhard H. Dick, Sebastian Pirro, Panagoitis Laspas, Franz H. Grus; Importance Of Autoreactive Antibodies For Retinal Ganglion Cell Loss In A Model Of Experimental Autoimmune Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2447.
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© ARVO (1962-2015); The Authors (2016-present)
Antibodies against retinal antigens occur in patients with glaucoma. Previous studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immune-mediated retinal ganglion cell (RGC) loss in rodents.
Lewis rats were immunized with a retinal ganglion cell layer homogenate (RGA, n=10) and compared to controls (CO, n=10). RGC density was quantified using cresyl stained retinal flatmounts after six weeks. Retina and optic nerve cross-sections were used for detection of autoreactive antibodies, antibody depositions, and microglia cells (via anti-Iba 1 antibody). Depositions and microglia were counted on all cross-sections. A scoring system, ranging from 0=no DAB staining to 3=strong staining, was applied for the intensity of the autoreactive antibody stain. A possible retinal gliosis was also analyzed, using anti-GFAP antibody. Severity of gliosis was scored by three examiners, scores ranging from 0=no staining, to 3=strong GFAP positive staining. The two groups were compared via t-test. Additionally, brain sections were analyzed for possible pathological findings.
Immunization with RGA did only lead to a reduced retinal ganglion cell density (p=0.007) but also to antibody deposits in the retina (RGA: 3.0±0.5/mm; CO=1.3±0.3/mm). An increase in autoreactive antibodies occurred in retinas after immunization, at six weeks a mean score of 4±0.3 was observed for the RGA group compared to 0.3±0.1 for controls (p=0.004). Additionally, we detected a reactive Müller cell gliosis (scores: RGA=2.03±0.1, CO=1.3±0.2; p=0.001) as well as the invasion of activated microglia cells (RGA: 6.3±0.9 cells/mm, CO: 2.2±0.2 cells/mm; p=0.005). Observations of the CNS revealed no pathological aberrations, such as inflammatory infiltrates, demyeliniation or hemorrhages.
Our findings suggest that autoreactive antibodies play a substantial role in mechanisms leading to retinal ganglion cell death, possibly through binding to RGCs and therefore triggering apoptosis. RGC loss seems to lead to Müller cell activation as well as the invasion of activated microglia, which might be associated with debris clearance.
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