Hisano Suguru, Koriyama Yoshiki, Ogai Kazuhiro, Sugitani Kayo, Kato Satoru
Department of Clinical Laboratory Science, Department of Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan.
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Sciences, 3500-3 Minamitamagaki, 513-8670, Suzuka, Japan.
Adv Exp Med Biol. 2016;854:379-84. doi: 10.1007/978-3-319-17121-0_50.
Retinal degeneration (RD) such as retinitis pigmentosa and age-related macular degeneration are major causes of blindness in adulthood. As one of the model for RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used because of its selective photoreceptor cell death. It has been reported that MNU increases intracellular calcium ions in the retina and induces photoreceptor cell death. Although calcium ion influx triggers the neuronal nitric oxide synthase (nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not been reported yet. In this study, we investigated the contribution of nNOS on photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS activation at 3 day after treatment. Then, we evaluated the effect of nNOS specific inhibitor, ethyl[4-(trifluoromethyl) phenyl]carbamimidothioate (ETPI) on the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the MNU-induced cell death in the ONL. These data indicate that nNOS is a key molecule for pathogenesis of MNU-induced photoreceptor cell death.
视网膜变性（RD），如色素性视网膜炎和年龄相关性黄斑变性，是成年人失明的主要原因。作为RD的模型之一，腹腔注射N-甲基-N-亚硝基脲（MNU）因其选择性光感受器细胞死亡而被广泛应用。据报道，MNU会增加视网膜内的细胞内钙离子并诱导光感受器细胞死亡。虽然钙离子内流会触发神经元型一氧化氮合酶（nNOS）的激活，但nNOS在MNU诱导的光感受器细胞死亡中的作用尚未见报道。在本研究中，我们调查了nNOS在MNU诱导的小鼠光感受器细胞死亡中的作用。MNU在治疗后3天显著增加了NOS的激活。然后，我们评估了nNOS特异性抑制剂乙基[4-（三氟甲基）苯基]氨基硫代甲脒（ETPI）对MNU诱导的光感受器细胞死亡的影响。在3天时，ETPI明显抑制了MNU诱导的外核层细胞死亡。这些数据表明，nNOS是MNU诱导的光感受器细胞死亡发病机制中的关键分子。
