Department of Ophthalmology, The 900th Hospital of Joint Logistic Support Force, PLA (Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University), Fuzhou, 350025, China.
Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
BMC Ophthalmol. 2020 Feb 18;20(1):55. doi: 10.1186/s12886-020-1330-8.
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.
色素性视网膜炎（RP）是一种遗传性视网膜退行性疾病，其特征是感光细胞逐渐丧失。直到现在，RP 仍然是临床没有令人满意对策的难题。乙醛脱氢酶 2（ALDH2）是一种主要参与醛解毒的酶，已被证明对越来越多的人类疾病有益，如心血管功能障碍、糖尿病和神经退行性变。然而，其对 RP 的保护作用尚不清楚。我们的研究探讨了 ALDH2 对 N-甲基-N-亚硝脲（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，用 5mg/kg 的 Alda-1（ALDH2 激动剂）灌胃大鼠。进行视网膜功能和形态评估以及特定蛋白质表达水平的测量。
视网膜电图记录显示，Alda-1 给药减轻了 MNU 引起的振幅降低，从而保护了视网膜功能。光学相干断层扫描和视网膜组织学检查观察到 MNU 处理的视网膜中光感受器变性减轻。此外，Western blot 结果显示，ALDH2 蛋白表达水平上调，Alda-1 干预后 SIRT1 蛋白表达增加。此外，GRP78 蛋白的显著下调表明内质网应激（ERS）减少，而 PARP1 蛋白表达减少表明细胞凋亡得到改善。
总之，我们的数据表明，ALDH2 可以提供对 MNU 诱导的 RP 的视网膜功能和形态的保护，其潜在机制至少部分与 SIRT1、ERS 和细胞凋亡的调节有关。
