Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats. Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted. Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein. Together, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.

中文翻译：

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ALDH2对MNU诱导的色素性视网膜炎大鼠视网膜功能和形态的保护：一项体内研究

色素性视网膜炎（RP）是一种以光感受器进行性丧失为特征的遗传性视网膜变性疾病。到目前为止，RP在临床上还没有令人满意的对策，这一直是一个难题。乙醛脱氢酶2（ALDH2）是一种参与醛解毒的主要酶，已被证明对越来越多的人类疾病（如心血管功能障碍，糖尿病和神经退行性疾病）有益。但是，其对RP的保护作用仍然未知。我们的研究探讨了ALDH2对N-甲基-N-亚硝基脲（MNU）诱导的RP大鼠视网膜功能和结构的影响。在MNU给药前5天和给药后3天，给大鼠灌胃5 mg / kg Alda-1（一种ALDH2激动剂）。进行了视网膜功能和形态的评估以及特定蛋白质表达水平的测量。视网膜电图记录表明，Alda-1给药减轻了由MNU引起的振幅下降，从而保护了视网膜功能。通过光学相干断层扫描和视网膜组织学检查，可以观察到MNU处理的视网膜中感光细胞变性的减轻。此外，蛋白质印迹结果表明，Alda-1干预后，ALDH2蛋白表达水平随SIRT1蛋白表达的增加而上调。此外，GRP78蛋白的显着下调可降低内质网应激（ERS），而PARP1蛋白表达的降低则表明细胞凋亡得到改善。一起，