Comparative gene array analysis of TNF-alpha-induced MAPK and NF-kappaB signaling pathways between retinal ganglion...

TNF-alpha has recently been identified to be a mediator of retinal ganglion cell (RGC) death, while glial cells are relatively protected against this death stimulus. To identify molecular mechanisms that control diverse responses of RGCs and glial cells to TNF-alpha, we studied differential gene expression between primary cultures of RGCs and glial cells exposed to TNF-alpha using cDNA array analysis of MAPK and NF-kappaB signaling pathways. Findings of this comparative analysis demonstrated differential regulation of various genes between RGCs and glial cells exposed to TNF-alpha. RT-PCR confirmed the differential expression of selected genes, and immunocytochemistry demonstrated gene products in cultured cells. Immunolabeling with phosphorylation site-specific antibodies also revealed differential post-translational modifications of selected proteins between cell types. Identification of signaling molecules differentially regulated in RGCs and glial cells can improve our understanding of the diverse cellular responses and provide targets for neuroprotective interventions in several neurodegenerative conditions.