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Abstract #13747 Published in IGR 8-2
Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion
Lieven CJ; Hoegger MJ; Schlieve CR; Levin LAInvestigative Ophthalmology and Visual Science 2006; 47: 1477-1485
See also comment(s) by Keith Martin •
PURPOSE: Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. The time course of cell death is variable and depends in part on the degree of injury sustained. Decreasing reactive oxygen species (ROS) levels or shifting the redox state to reduction promotes the survival of RGCs in tissue culture after axotomy. It was hypothesized that a specific ROS, superoxide anion, acts as an intracellular signaling molecule for RGC death after axotomy. METHODS: Intracellular superoxide levels were measured after dissociation in retrograde-labeled rat RGCs with use of the superoxide-sensitive fluorophores hydroethidium and MitoSOX Red. Having found a significant increase, the effect of axotomy was determined on superoxide levels independent of dissociation with an optic nerve crush model. RESULTS: Optic nerve crush caused RGCs to undergo a superoxide burst. The burst was asynchronous and was manifested in only a fraction of cells at any given time. Neurotrophin deprivation was not responsible for the superoxide burst because it was not prevented by incubation with the neurotrophic factors brain-derived neurotrophic factor, ciliary neurotrophic factor, forskolin, or insulin. Several inhibitors of intracellular superoxide generation were studied, but only antimycin A, which inhibits complex III of the mitochondrial electron transport chain, blocked the increase in superoxide. CONCLUSIONS: These findings suggest that superoxide generated in the mitochondrial electron transport chain could be a parallel system to neurotrophic deprivation for signalling cell death after axonal injury.
Dr. C.J. Lieven, Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA
Classification:
5 Experimental glaucoma; animal models
