Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo |
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Authors: | Weishaupt J H Diem R Kermer P Krajewski S Reed J C Bähr M |
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Affiliation: | Department of Neurology, University Hospital G?ttingen, Robert-Koch-Strasse 40, 37075 G?ttingen, Germany. jweisha@gwdg.de |
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Abstract: | We have investigated the role of caspase-8 and its mode of activation during apoptosis of adult rat retinal ganglion cells (RGCs) in vivo. Retinal pro-caspase-8 expression was almost completely restricted to RGCs. Although caspase-8 is known to be involved in death-receptor-dependent apoptosis, measurable caspase-8 activity or even RGC death could be induced by neither tumor necrosis factor-alpha nor Fas ligand injections into unlesioned eyes. However, substantial caspase-8 activation could be detected after optic nerve transection as shown by a fluorogenic activity assay and Western blot analysis. Intravitreal injection of caspase-8 inhibitors significantly attenuated degeneration of RGCs and reduced the number of RGCs showing caspase-3 activation. A late peak of caspase-8 activity and additive protective effects of caspase-8 and -9 inhibition on axotomized RGCs place caspase-8 in our model rather late in the apoptosis cascade, possibly after the onset of mitochondrial dysfunction. |
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