Contributions
Abstract: P995
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Background: Autoimmune optic neuritis (AON), induced by immunisation of Brown Norway rats with myelin oligodendocyte glycoprotein (MOG), has been shown to mimic many pathological aspects of multiple sclerosis (MS). Previously, we showed that prior to inflammatory demyelination and axonal loss within the optic nerves, neurodegeneration of retinal ganglion cells and ultrastructural changes in their still myelinated axons could be observed. This occurred in parallel with microglial activation, particularly in the optic nerve head (ONH). These responses are similar to those reported in preactive MS lesions, where clusters of activated microglia appear in the absence of demyelination or leukocyte infiltration, and are accompanied by increased expression of the heat shock protein alpha B-crystallin (cryαb) in oligodendrocytes. Due to these similarities, we wished to determine if cryαb is similarly upregulated during the onset of AON.
Results: Although apoptosis of oligodendrocytes could not be detected prior to the onset of inflammatory demyelination, increased levels of cryαb in optic nerve lysates and its expression in oligodendrocytes was observed already during the induction phase of AON, particularly in the ONH area. Since we have previously shown this area to be partially permeable to blood-derived factors such as autoantibodies, we wished to determine whether the deposition of autoantibodies alone could induce oligodendrocyte stress in this area. To address this, sera was transferred from MOG-immunised animals into naïve recipients, and cryαb expression was assessed. Anti-MOG antibody levels were detectable in the sera of recipient rats for up to 5 days post-serum transfer (although at considerably lower levels than in actively immunised animals), and its deposition was also observed within the ONH. Although major signs of optic nerve pathology (such as inflammatory demyelination) were not seen in recipient animals, the presence of oligodendrocyte stress, observed by increased presence of cryαB, could be detected in the area of the ONH in a similar manner to that observed in the induction phase of AON.
Conclusion: Cryαb upregulation is an early event during AON, being expressed mainly by oligodendrocytes and particularly in the vicinity of the ONH. Investigation of recipients following sera transfer from MOG-immunised rats suggest that this is, at least in part, mediated by the entry of circulating anti-MOG antibodies through the partially permeable ONH.
Disclosure: This study was supported by the Hertie Foundation and the German Research Foundation (FOR2289).
Stojic A.: nothing to declare
Abstract: P995
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Background: Autoimmune optic neuritis (AON), induced by immunisation of Brown Norway rats with myelin oligodendocyte glycoprotein (MOG), has been shown to mimic many pathological aspects of multiple sclerosis (MS). Previously, we showed that prior to inflammatory demyelination and axonal loss within the optic nerves, neurodegeneration of retinal ganglion cells and ultrastructural changes in their still myelinated axons could be observed. This occurred in parallel with microglial activation, particularly in the optic nerve head (ONH). These responses are similar to those reported in preactive MS lesions, where clusters of activated microglia appear in the absence of demyelination or leukocyte infiltration, and are accompanied by increased expression of the heat shock protein alpha B-crystallin (cryαb) in oligodendrocytes. Due to these similarities, we wished to determine if cryαb is similarly upregulated during the onset of AON.
Results: Although apoptosis of oligodendrocytes could not be detected prior to the onset of inflammatory demyelination, increased levels of cryαb in optic nerve lysates and its expression in oligodendrocytes was observed already during the induction phase of AON, particularly in the ONH area. Since we have previously shown this area to be partially permeable to blood-derived factors such as autoantibodies, we wished to determine whether the deposition of autoantibodies alone could induce oligodendrocyte stress in this area. To address this, sera was transferred from MOG-immunised animals into naïve recipients, and cryαb expression was assessed. Anti-MOG antibody levels were detectable in the sera of recipient rats for up to 5 days post-serum transfer (although at considerably lower levels than in actively immunised animals), and its deposition was also observed within the ONH. Although major signs of optic nerve pathology (such as inflammatory demyelination) were not seen in recipient animals, the presence of oligodendrocyte stress, observed by increased presence of cryαB, could be detected in the area of the ONH in a similar manner to that observed in the induction phase of AON.
Conclusion: Cryαb upregulation is an early event during AON, being expressed mainly by oligodendrocytes and particularly in the vicinity of the ONH. Investigation of recipients following sera transfer from MOG-immunised rats suggest that this is, at least in part, mediated by the entry of circulating anti-MOG antibodies through the partially permeable ONH.
Disclosure: This study was supported by the Hertie Foundation and the German Research Foundation (FOR2289).
Stojic A.: nothing to declare