Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD⁺), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL⁺ photoreceptors, CD11b⁺ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD⁺ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.

中文翻译：

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烟酰胺光变性视网膜脱离模型中烟酰胺单核苷酸（NMN）的神经保护作用和作用机制

目前，没有药物疗法被证明可有效治疗患者的感光细胞变性。因此，人们迫切需要发现容易获得且安全的神经保护剂。在这里，我们在视网膜脱离（RD）引起的感光细胞变性中研究了烟酰胺单核苷酸（NMN）（烟酰胺腺嘌呤二核苷酸（NAD ⁺）的前体）。RD后NMN给药导致TUNEL ⁺感光细胞，CD11b ⁺巨噬细胞和GFAP标记的神经胶质细胞活化显着降低；蛋白质羰基含量（PCC）的标准化，以及外核层（ONL）厚度的保留。NMN管理显着增加了NAD ⁺水平，SIRT1蛋白表达和血红素加氧酶1（HO-1）表达。RD后NMN延迟给药仍然发挥保护作用。使用661W细胞进行的体外机制研究显示，SIRT1 / HO-1信号作为NMN介导的氧化应激和LPS刺激保护的下游效应子。总之，NMN给药对RD和氧化损伤后的感光细胞具有神经保护作用，为治疗感光细胞变性提供了治疗途径。