ラット培養網膜神経節細胞における一酸化窒素合成酵素阻害剤の細胞保護効果
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概要
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Nitric oxide may mediate excitotoxic and ischemic effects on central neurons. This study investigated the effect of a nitric oxide synthase (NOS) inhibitor on the survival of cultured rat retinal ganglion cells (RGCs) subjected to hypoxia and excitotoxicity. Dissociated RGCs from neonatal rats were plated on an anti-glial fibrillary acidic protein positive glial cell monolayer after they were retrogradely labeled with the fluorescent marker DiI. The glial cell monolayer is bNOS positive and iNOS negative immunohistochemically. Two days after dissociation, they were treated with graded concentrations of the NOS inhibitor Nco-nitro-L-arginine (NA), and exposed to hypoxia for from 1 to 24 hours or to excitatory amino acids. The number of surviving RGCs were counted under fluorescein microscopy after a 24-hour recovery period, and were expressed as a percentage of RGCs surviving compared to a control group. The survival rate of cultured RGCs exposed to hypoxia increased in a dose-dependent fashion with NA. The time course of the survival rate of RGC cultures pretreated with NA showed a better survival rate. The survival rate of the cultured RGCs exposed to excitatory amino acid was lower than that of the RGCs pretreated with NA. A NOS inhibitor provides partial protection of RGCs against hypoxia and excitotoxicity in cell culture. The results in this model suggest that protection is conferred at the cellular level.
- 東京女子医科大学の論文
- 2001-06-25