Yan Weiming, Sun Yan, Wang Yutong, Liang Wangjiao, Xia Yuxin, Yan Weihua, Chen Meizhu, Chen Tao, Li Dongliang
Department of Ophthalmology, The 900th Hospital of Joint Logistic Support Force, PLA (Clinical Medical College of Fujian Medical University, Dongfang Hopsital Affiliated to Xiamen University), Fuzhou, People's Republic of China.
Center of Clinical Aerospace Medicine, Air Force Military Medical University, Xi'an, People's Republic of China.
Anim Cells Syst (Seoul). 2023 Jun 26;27(1):138-148. doi: 10.1080/19768354.2023.2226695. eCollection 2023.
Upregulation of Sirtuin Type 1 (SIRT1), a nicotinamide adeninedinucleotide (NAD)-dependent deacetylase, has been proved to protect against ample ocular diseases, while its effect on retinitis pigmentosa (RP) has not been illustrated. The study was aimed to explore the impacts of resveratrol (RSV), a SIRT1 activator, on the photoreceptor degeneration in a rat model of RP induced by N-methyl-N-nitrosourea (MNU), an alkylation. The rats were induced RP phenotypes via the intraperitoneal injection of MNU. The electroretinogram was conducted and revealed that RSV could not prevent the decline of retinal function in the RP rats. The optical coherence tomography (OCT) and the retinal histological examination were performed and showed that the reduced thickness of the outer nuclear layer (ONL) was not preserved by RSV intervention. The immunostaining technique was applied. Afther the MNU administration, the number of the apoptotic photoreceptors in the ONL throughout the retinasand the number of microglia cells present among the outer part throughout the retinas were not significantly reduced by RSV. Western blotting was also performed. The data showed that the level of SIRT1 protein was decreased after MNU administration, while RSV was not able to obviously alleviate the downregulation. Our data together indicated that RSV was not able to rescue the photoreceptor degeneration in the MNU-induced RP rats, which might be due to the MNU-induced consumption of the NAD.
1型沉默调节蛋白（SIRT1）是一种烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱乙酰酶，其上调已被证明可预防多种眼部疾病，但其对视网膜色素变性（RP）的影响尚未阐明。本研究旨在探讨SIRT1激活剂白藜芦醇（RSV）对N-甲基-N-亚硝基脲（MNU，一种烷基化剂）诱导的RP大鼠模型中光感受器变性的影响。通过腹腔注射MNU诱导大鼠出现RP表型。进行视网膜电图检查，结果显示RSV不能阻止RP大鼠视网膜功能的下降。进行光学相干断层扫描（OCT）和视网膜组织学检查，结果表明RSV干预未能维持外核层（ONL）厚度的减少。应用免疫染色技术。给予MNU后，RSV并未显著减少整个视网膜ONL中凋亡光感受器的数量以及整个视网膜外部区域中存在的小胶质细胞的数量。还进行了蛋白质免疫印迹分析。数据显示，给予MNU后SIRT1蛋白水平降低，而RSV不能明显缓解这种下调。我们的数据共同表明，RSV不能挽救MNU诱导的RP大鼠中的光感受器变性，这可能是由于MNU诱导的NAD消耗所致。
