Physiological significance of Rag1 in optic nerve neuropathy

Although the transcription factor, nuclear factorB (NFB) is known to regulate cell death and survival, its precise role in cell death within the central nervous system (CNS) remains unknown. We previously reported that mice with a homozygous deficiency for NFBp50 spontaneously developed optic neuropathy. We studied the expression and activation of pro-apoptotic factor(s), which mediate optic nerve neuropathy in p50-null mice. Recombination activating gene 1 (Rag1) is known to control the recombination of immunoglobulin V(D)J. Experiments with genetically engineered mice revealed the involvement of Rag1 expression in the apoptosis of Brn3a-positive retinal ganglion cells (RGCs), and also showed the specific effects of a p50-null on the activation of Rag1 gene transcription. Furthermore, a genetic analysis of murine neuronal stem-like cells clarified the biological significance of Rag1 in N-methyl-D-aspartate (NMDA)induced neuronal cell death. The apoptotic inducing factors, Bax, and cleaved caspase 3, 8, and 9 were detected in HEK293 cells expressing the external molecule of Rag1, and a human histopathological examination revealed the expression of Rag1 in RGCs. Recent studies indicated that Rag1 played a role in optic nerve neuropathy as a pro-apoptotic candidate in p50-null mice. These results may lead to new therapeutic targets in optic nerve neuropathy. KEYWORDS