PURPOSE: Multiple studies indicate that T-cells play a major role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, but recently an involvement of antibodies has also been discussed. The aim of our study was to examine the effects of myelin basic protein (MBP) immunization on survival of neurons, alteration of antibody reactivity, and microglia in the retinal ganglion cell layer. METHODS: EAE was induced in rats by immunization with MBP. Intraocular pressure (IOP) measurements and funduscopies were performed regularly. Neuron cell density was evaluated on cresyl-stained retinal flatmounts. IgG antibody deposition and activated microglia were detected in retina and optic nerve sections via immunohistology. The intensity of autoreactive IgG antibodies was quantified in successive serum samples via tissue arrays. RESULTS: Significant loss of neurons was detected 6 weeks after immunization (p < 0.05). At the same time, IgG antibody deposits accumulated in the retina and the optic nerve of EAE animals and a significant microglia turn-over to activation was observed. The level of IgG antibody reactivity against retina and optic nerve tissue continuously increased (p < 0.05). While clinical parameters indicated typical EAE progression, we observed no changes in IOP (p > 0.9) or abnormalities in fundi. CONCLUSIONS: Immunization with MBP not only causes neuron loss in the retinal ganglion cell layer, but also triggers antibody reactivity against ocular tissue. Possibly some of these antibodies are involved in the induction of neuronal apoptosis. This study suggests that, apart from T-cell mediation, alteration of antibody reactivity and activated microglia do also influence the ocular pathomechanisms in the EAE model.
PURPOSE: Multiple studies indicate that T-cells play a major role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, but recently an involvement of antibodies has also been discussed. The aim of our study was to examine the effects of myelin basic protein (MBP) immunization on survival of neurons, alteration of antibody reactivity, and microglia in the retinal ganglion cell layer. METHODS: EAE was induced in rats by immunization with MBP. Intraocular pressure (IOP) measurements and funduscopies were performed regularly. Neuron cell density was evaluated on cresyl-stained retinal flatmounts. IgG antibody deposition and activated microglia were detected in retina and optic nerve sections via immunohistology. The intensity of autoreactive IgG antibodies was quantified in successive serum samples via tissue arrays. RESULTS: Significant loss of neurons was detected 6 weeks after immunization (p < 0.05). At the same time, IgG antibody deposits accumulated in the retina and the optic nerve of EAE animals and a significant microglia turn-over to activation was observed. The level of IgG antibody reactivity against retina and optic nerve tissue continuously increased (p < 0.05). While clinical parameters indicated typical EAE progression, we observed no changes in IOP (p > 0.9) or abnormalities in fundi. CONCLUSIONS: Immunization with MBP not only causes neuron loss in the retinal ganglion cell layer, but also triggers antibody reactivity against ocular tissue. Possibly some of these antibodies are involved in the induction of neuronal apoptosis. This study suggests that, apart from T-cell mediation, alteration of antibody reactivity and activated microglia do also influence the ocular pathomechanisms in the EAE model.
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