Failure to activate NF-kappaB promotes apoptosis of retinal ganglion cells following optic nerve transection.

Abstract

NF-kappaB is a transcription factor, which is activated by various stimuli. One of the well-known activators of NF-kappaB is oxidative stress, which is a cause of cell death in some tissue, or cell types. Optic nerve transection, axotomy, results in retinal cell death, because of oxidative stress, deprivation of neurotrophic factors, etc. Since it has been hypothesized that the retinal ganglion cell death after axotomy is due to the generation of reactive oxygen species, we investigated whether NF-kappaB is involved in the retinal cell death after axotomy. This study was performed to investigate the role of NF-kappaB in retinal ganglion cell death after optic nerve transection. We used double staining experiment by using anti-NF-kappaB antibody and ethidium bromide to observe the correlation of NF-kappaB activation and the cell death. NF-kappaB was observed only in the surviving cells. NF-kappaB translocation was observed 3 days after the optic nerve transection. The NF-kappaB inhibitor, sulfasalazine, was used to block the activation of NF-kappaB in the axotomized retina, and the number of ganglion cells was quantified using retrograde in the presence or absence of sulfasalazine after axotomy. Inhibition of NF-kappaB by sulfasalazine accelerated the degeneration of ganglion cells in the retina. The results suggest that the activated NF-kappaB plays a protective role from the cell death in the injured ganglion cells.