Activation inhibitors of nuclear factor kappa B protect neurons against the NMDA-induced damage in the rat retina

We reported that high-mobility group box-1 (hmgb1) was involved in excitoneurotoxicity in the retina. hmgb1 is known to activate nuclear factor kappa b (nf-κb). however,the role of nf-κb in excitotoxicity is still controversial. here,we demonstrated that nf-κb activation induced by nmda led to the retinal neurotoxicity. male sprague–dawley rats were used,and nmda (200 nmol/eye) and bovine hmgb1 (15 μg/eye) were intravitreally injected. triptolide (500 pmol/eye),bay 11-7082 (500 pmol/eye),and imd-0354 (7.5 nmol/eye),nf-κb inhibitors,were co-injected with nmda or hmgb1. retinal sections were obtained seven days after intravitreal injection. cell loss in the ganglion cell layer was observed in the hmgb1- and the nmda-treated retina. all of the nf-κb inhibitors used in this study reduced the damage. bay 11-7082 reduced the expression of phosphorylated nf-κb 12 h after nmda injection,upregulation of gfap immunoreactivity induced by nmda 12 and 48 h after nmda injection,and the number of tunel-positive cells 48 h after nmda injection. the results suggest that nf-κb activation is one of the mechanisms of the retinal neuronal death that occurs 48 h after nmda injection or later. prevention of nf-kb activation is a candidate for the treatment of retinal neurodegeneration associated with excitotoxicity. © 2017 the authors