Volume : 3, Issue : 4, April - 2014

Development of spontaneous optic neuropathy in NF – kBp50–deficient mice

Takuma Hayashi, Toshinori Murata

Abstract :

Although the transcription factor, nuclear factor-kappa B (NF-kB) is known to regulate cell death and survival, its precise role in neuronal cell death within the central nervous system remains unknown. The purpose of this study was to investigate the role of NF-kBp50 in the age-related survival of retinal ganglion cells (RGCs). Eyes of mice with a deleted NF-kBp50 gene and its wild-type mice at each of age were studied by histopathological studies. The number of RGCs was counted using retrograde labelling methods. Mice were subjected to intravitreous injection of N-methyl-D aspartate (NMDA) to induce RGC death. In NF-kBp50-deficient mice, the number of RGCs significantly decreased with age in total independence of intraocular pressure measurement. Optic nerves of p50-deficient mice showed hypertrophy astrocytes and enlargement of the axons, together with a decreased number of axons. Immunohistochemistry (IHC) showed a strong expression of glial fiillary acidic protein. The histological results show obvious excavation of the optic nerve head in NF-kBp50-deficient mice at 10 months of age. Intravitreal injection of NMDA in young p50-deficient mice damaged RGCs more intensively than in control animals. We further noticed that auto-antibodies against RGCs were produced in NF-kBp50-deficient mice. Our results show that p50 deficiency induced age related RGC death, indicating a new insight into the role of p50 in the pathophysiology of neuropathy, and further experiments with NF-kBp50-deficient mice may provide new targets for therapeutic intervention for human glaucoma.