Spontaneous Optic Neuropathy: Involvement of NF-B Activation by the Calcineurin Signal Cascade
Journal: Palliative Medicine And Nursing: Open Access (Vol.2, No. 1)Publication Date: 2015-11-03
Authors : Takuma Hayashi Tomoko Nakamura-Yanagidaira Takao Hirano; Toshinori Murata;
Page : 1-8
Keywords : NF-B; p50; Calcineurin; Glaucoma; NTG;
Abstract
Members of the nuclear factor-kappa B (NF-B)/Rel family, which act as transcriptional regulators, play important roles in neuronal cell death and survival. NF-Bp50 knockout (p50-KO) mice exhibit many of the features of human Normal Tension Glaucoma (NTG). The developmental mechanism of human NTG remains unclear, and a radical curative treatment has yet to be established. Therefore, the signal cascade that mediates spontaneous optic neuropathy in p50-KO mice, as a model of NTG, needs to be elucidated in more detail for the development of clinical therapies. In order to obtain a deeper understanding of NF-B-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy have been examined histopathologically. Constitutively active cleaved forms of Calcineurin (CN), which have been reported to induce apoptosis, were detected in the retinas of p50-KO mice. Spontaneous retinal Ganglion Cell (RGC) death and degenerative changes to the optic nerve in p50-KO mice were both significantly reduced by the chronic administration of tacrolimus, a CN inhibitor. Experiments with cultured RGC cells supported the results of histological examinations on p50-KO mice, suggesting that CN activation leads to the activation of NF-B-induced Bax and caspase 3 and mediates spontaneous optic neuropathy in p50-KO mice. Previous studies demonstrated that the chronic administration of tacrolimus significantly reduced spontaneous optic neuropathy in p50-KO mice. A potential CN signal cascade spontaneously induces agedependent RGC death and degenerative optic nerve changes in p50-KO mice. Novel research findings may provide new targets for therapeutic interventions in human NTG
Other Latest Articles
- Epidemiological Analysis of Congenital Cataract in a Sample of Iraqi Patients
- Spontaneous Optic Neuropathy: Involvement of NF-B Activation by the Calcineurin Signal Cascade
- Challenges of Clinical Research in Physical Medicine & Rehabilitation: Considerations from a Working Group from Brazil, USA and Canada
- The Relation to Effective Communication on Cancer among Patients and the Families on Psychological Adaptation between Japanese Chemotherapy-Treated Outpatients and their Family Members
- QRT-PCR is a Highly Sensitive, Highly Specific Diagnostic Adjunct to H&E Microscopy to Detect Giardia Using Formalin-Fixed Paraffin-Embedded Tissue
Last modified: 2018-10-05 18:14:23