Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

Published

Journal Article

Purpose: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). Methods: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). Results: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. Conclusions: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.

Full Text

Duke Authors

Cited Authors

  • Smit-McBride, Z; Nguyen, J; Elliott, GW; Wang, Z; McBride, RA; Nguyen, AT; Oltjen, SL; Yiu, G; Thomasy, SM; Pinkerton, KE; Lee, ES; Cunefare, D; Farsiu, S; Morse, LS

Published Date

  • January 2018

Published In

Volume / Issue

  • 24 /

Start / End Page

  • 633 - 646

PubMed ID

  • 30294202

Pubmed Central ID

  • 30294202

Electronic International Standard Serial Number (EISSN)

  • 1090-0535

International Standard Serial Number (ISSN)

  • 1090-0535

Language

  • eng