title: Nuclear factor-kappa B p65 in NMDA-induced retinal neurotoxicity.
abstract: Transcription factors of the nuclear factor-kappa B (NF-kappaB)/Rel family may be involved in neuronal cell death or survival. We examined the role of NF-kappaB p65 in N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. Western blot analysis showed that elevated levels of retinal NF-kappaB p65 protein at days 1 and 5 after intravitreal NMDA injection. Immunohistochemistry localized increased NF-kappaB p65 immunoreactivity in the ganglion cell layer (GCL) and the inner nuclear layer (INL) after NMDA injection especially in retinal ganglion cells (RGCs), displaced amacrine cells, and amacrine cells. Concomitant with the early increase in NF-kappaB p65 protein levels, there was an increase in NF-kappaB DNA binding activity after NMDA injection as shown by electrophoretic mobility shift assay (EMSA). These increases in NF-kappaB p65 protein levels and NF-kappaB DNA binding activity were totally abolished by simultaneous injection of NF-kappaB p65 antisense oligodeoxynucleotide (AS ODN). A partial but significant protective effect on the inner retina was noted when the AS ODN was given together with NMDA as shown by morphological analysis, morphometry of cells in the GCL and morphometry of inner plexiform layer thickness as well as quantitative real-time PCR of Thy-1 mRNA levels. These results suggest that activated NF-kappaB p65 may participate in NMDA-induced retinal neuronal cell death and that inhibition of NF-kappaB activation such as the use of AS ODN may be a viable neuroprotective strategy for protective RGCs and other inner retinal neurons.
authors.affiliation: Department of Ophthalmology, St Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan. kitaoka@marianna-u.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaoka
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kitaoka
authors.forename: Tim T
authors.initials: TT
authors.lastname: Lam
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Munemasa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Isenoumi
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Motoki
authors.forename: Kohei
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Jiro
authors.initials: J
authors.lastname: Kogo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Satoki
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000633:toxicity*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy; D051996:Transcription Factor RelA
chemical_list: D018690:Excitatory Amino Acid Agonists; D016328:NF-kappa B; D018696:Neuroprotective Agents; D020319:Oligodeoxyribonucleotides, Antisense; D051996:Transcription Factor RelA; D016202:N-Methylaspartate