Abstract
Abstract: :
Purpose: The Nuclear Factor (NF)-ΚB is an essential transcriptional regulator for genes involved in cell death. The role of NF-ΚB on the fate of retinal ganglion cells (RGCs), the neuronal population that dies in glaucoma, remains undefined. We investigated the endogenous expression of two predominant subunits of NF-ΚB: p65 (RelA) and p50 (NFΚB1) and the inhibitory protein IΚB-α in intact and injured adult retinas. Methods: Cellular localization of p65, p50 and IΚB-α proteins were visualized by immunocytochemistry. Radial sections were generated from intact retinas or retinas subjected to one of the following: i) optic nerve transection, ii) intravitreal injection of NMDA, or iii) intravitreal injection of BDNF. Changes in NF-ΚB expression were examined prior to the onset of RGC death. For co-localization studies, RGCs were labeled by application of FluoroGold to both superior colliculi. In addition, we used Müller cell- and astrocyte-specific markers. Results: The following expression pattern of endogenous NF-ΚB components was found in the intact retina: i) most RGCs and cells in the inner nuclear layer showed p50-positive immunoreactivity, ii) in contrast, only few RGCs and astrocytes in the ganglion cell layer had p65 immunolabeling; and iii) the IΚB-α protein was expressed only in Müller cell processes and end-feet. Following optic nerve transection, there was a marked increase in the number of p65-positive astrocytes of the ganglion cell layer. NMDA injection produced upregulation of IΚB-α staining in Müller cell processes. Interestingly, intravitreal injection of BDNF markedly increased the number of RGCs expressing p65. The immunolabeling pattern of p50 remained unchanged after axotomy and NMDA or BDNF injection. Conclusions: Injury modalities that lead to RGC death induced upregulation of the NF-ΚB components, p65 and IΚB-α, in retinal glial cells. In contrast, the neuroprotective factor BDNF markedly increased the number of RGCs expressing p65. These data suggest a correlation between NF-ΚB expression in retinal glia and RGC death, while neuronal expression of NF-ΚB may be associated with RGC survival.
Keywords: transcription factors • ganglion cells • neuroprotection