Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo
2003 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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- Authors
- Weishaupt, J. H. ; Diem, R. ; Kermer, P. ; Krajewski, S.; Reed, J. C.; Bähr, M.
- 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-a 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. (C) 2003 Elsevier Science (USA). All rights reserved.
- Issue Date
- 2003
- Journal
- Neurobiology of Disease
- ISSN
- 0969-9961
- Language
- English