Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion.

Leonard Levin // Publications // Apr 01 2006

PubMed ID: 16565382

Author(s): Lieven CJ, Hoegger MJ, Schlieve CR, Levin LA. Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1477-85. PMID 16565382

Journal: Investigative Ophthalmology & Visual Science, Volume 47, Issue 4, Apr 2006

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 signaling cell death after axonal injury.