Nicotinamide Mononucleotide Prevents Retinal Dysfunction in a Mouse Model of Retinal Ischemia/Reperfusion Injury.

Nicotinamide Mononucleotide Prevents Retinal Dysfunction in a Mouse Model of Retinal Ischemia/Reperfusion Injury.
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DOI:
10.3390/ijms231911228
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发表时间:
2022-09-23
影响因子:
5.6
通讯作者:
Kurihara, Toshihide
Kurihara, Toshihide
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, Deokho;Tomita, Yohei;Miwa, Yukihiro;Shinojima, Ari;Ban, Norimitsu;Yamaguchi, Shintaro;Nishioka, Ken;Negishi, Kazuno;Yoshino, Jun;Kurihara, Toshihide

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视网膜缺血/再灌注(I/R)损伤可导致严重的视力障碍。视网膜I/R损伤与活性氧的病理性增加和炎症有关,导致视网膜神经细胞死亡。到目前为止,还没有开发出有效的治疗方法。烟酰胺单核苷酸(NMN)是烟酰胺腺嘌呤二核苷酸(NAD+)的重要中间体,已被证明对视网膜疾病具有神经保护作用。然而,目前尚不清楚NMN能否预防视网膜I/R损伤。因此,我们的目标是确定NMN治疗对视网膜I/R损伤所致的视网膜变性是否有效。成年小鼠腹腔注射NMN后1d,造成视网膜I/R损伤。然后,小鼠每天注射一次NMN,连续三天。视网膜电流图和免疫组织化学分别检测视网膜功能改变和视网膜炎症反应。在CoCl2诱导的氧化应激条件下,使用视网膜细胞系661W进一步检验了给予NMN的保护作用。NMN ip注射显著抑制视网膜功能损伤和炎症反应。NMN处理对氧化应激诱导的细胞死亡具有保护作用。NMN可激活抗氧化途径(Nrf2和Hmox-1)。综上所述,NMN可能是一种有前途的缺血性视网膜病变的预防性神经保护药物。
Retinal ischemia/reperfusion (I/R) injury can cause severe vision impairment. Retinal I/R injury is associated with pathological increases in reactive oxygen species and inflammation, resulting in retinal neuronal cell death. To date, effective therapies have not been developed. Nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD+) intermediate, has been shown to exert neuroprotection for retinal diseases. However, it remains unclear whether NMN can prevent retinal I/R injury. Thus, we aimed to determine whether NMN therapy is useful for retinal I/R injury-induced retinal degeneration. One day after NMN intraperitoneal (IP) injection, adult mice were subjected to retinal I/R injury. Then, the mice were injected with NMN once every day for three days. Electroretinography and immunohistochemistry were used to measure retinal functional alterations and retinal inflammation, respectively. The protective effect of NMN administration was further examined using a retinal cell line, 661W, under CoCl2-induced oxidative stress conditions. NMN IP injection significantly suppressed retinal functional damage, as well as inflammation. NMN treatment showed protective effects against oxidative stress-induced cell death. The antioxidant pathway (Nrf2 and Hmox-1) was activated by NMN treatment. In conclusion, NMN could be a promising preventive neuroprotective drug for ischemic retinopathy.
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