Smit-McBride Zeljka, Nguyen Johnny, Elliott Garrett W, Wang Zhe, McBride Ryan A, Nguyen Anthony T, Oltjen Sharon L, Yiu Glenn, Thomasy Sara M, Pinkerton Kent E, Lee Eugene S, Cunefare David, Farsiu Sina, Morse Lawrence S
Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, Davis, CA.
School of Veterinary Medicine, University of California, Davis, Davis, CA.
Mol Vis. 2018 Sep 24;24:633-646. eCollection 2018.
To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD).
All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA).
The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >±1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages.
ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.
确定环境烟草烟雾（ETS）对恒河猴血浆和眼内液中循环微小RNA（miRNA）的影响，并将这些变化与正常的年龄相关变化进行比较。烟草烟雾已被确认为年龄相关性黄斑变性（AMD）的主要环境危险因素。
所有恒河猴均饲养于加利福尼亚大学戴维斯分校的加利福尼亚国家灵长类动物研究中心（CNPRC）。使用了四组动物：第1组（1 - 3岁），第2组（19 - 28岁），第3组（10 - 16岁）和第4组（中年，9 - 14岁）。第4组暴露于烟雾中1个月。收集眼内液和血浆样本，分离miRNA，并使用Affymetrix miRNA GeneTitan Array Plates 4.0获得表达数据。在Affymetrix Expression Console（EC）、转录组分析软件（TAS）上进行生物信息学分析，使用方差分析（ANOVA）选择候选miRNA，随后进行 Ingenuity Pathway Analysis（IPA）。
循环miRNA的表达随年龄和ETS暴露呈现出统计学上的显著变化。在血浆样本中，45种miRNA在暴露于ETS后强烈上调（倍数变化>±1.5，p<0.05）。在玻璃体内，三种miRNA在暴露于ETS后统计学上显著下调，其中两种（miR - 6794和miR - 6790）在年龄增长时也统计学上显著下调。一些视网膜层通过光学相干断层扫描（OCT）成像测量显示出变薄趋势。激活的信号通路包括IL - 17A、VEGF以及嗜酸性粒细胞、Th2淋巴细胞和巨噬细胞的募集。
恒河猴暴露于ETS导致循环miRNA表达发生统计学上的显著变化，这与受衰老影响的变化不同。激活的信号通路似乎是ETS和AMD发病机制所共有的。这些数据将用于建立早期干性AMD的动物模型。
