91SPONTANEOUS OPTIC NEUROPATHY: BIOLOGICAL SIGNIFICANCE OF CALCINEURIN SIGNAL MOLECULE, NF-B.The transcriptional activator, nuclear factor-kappa B (NF-B)/Rel family are involved in neuronal cell death and survival. The mice with a targeted disruption of NF-Bp50 (p50-null mice) reportedly exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. It is important for developing clinical therapy to elucidate the signal pathway, which mediates the spontaneous optic neuropathy in p50-null mice as a model of NTG. To understand the NF-Bmediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological examinations. Further, the constitutively active cleaved forms of calcineurin (CALN), which have been reported to lead to cell death, were detected in the retina of p50-null mice. Both spontaneous retinal ganglion cell (RGC) death and degenerative changes to the optic nerve in p50-null mice were significantly reduced by the chronic administration of tacrolimus. The experiments with cultured RGC cells supported the results of histological studies with p50-null mice, suggesting that CALN activation leads to NF-B-induced Bax activation and caspase 3 activation, and mediates spontaneous optic neuropathy in p50-null mice. Research findings show that the chronic administration of tacrolimus, CALN inhibitor, significantly reduces spontaneous optic neuropathy in p50-null mice. A potential CALN signal pathway spontaneously induces age-dependent RGC death and degenerative optic nerve changes in p50-null mice. Novel research findings may provide new targets for therapeutic intervention in human NTG.yoyoyo224@hotmail.comResearch522015calcineurin,normal tension glaucoma,tacrolimus,retinal ganglion cellTakuma Hayashi,Tomoko Nakamura-Yanagidaira,Takao Hirano,Toshinori MurataDept. of Immunology and Infectious Disease,Shinshu University Graduate School of Medicine, Matsumoto, Japan,Department of Ophthalmology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.,Department of Ophthalmology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.,Department of Ophthalmology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.