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

Zeljka Smit-Mcbride, Johnny Nguyen, Garrett W. Elliott, Zhe Wang, Ryan A. McBride, Anthony T. Nguyen, Sharon L. Oltjen, Glenn Yiu, Sara M. Thomasy, Kent E. Pinkerton, Eugene S. Lee, David Cunefare, Sina Farsiu, Lawrence S. Morse

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)633-646
Number of pages14
JournalMolecular Vision
Volume24
StatePublished - Sep 24 2018

Fingerprint

Macaca mulatta
MicroRNAs
Smoke
Tobacco
Macular Degeneration
Down-Regulation
Interleukin-17
Optical Coherence Tomography
Gene Expression Profiling
Computational Biology
Eosinophils
Primates
Vascular Endothelial Growth Factor A
Analysis of Variance
Software
Animal Models
Macrophages
Lymphocytes
Research

ASJC Scopus subject areas

  • Ophthalmology

Cite this

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

In: Molecular Vision, Vol. 24, 24.09.2018, p. 633-646.

Research output: Contribution to journalArticle

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. / Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the rhesus macaque. In: Molecular Vision. 2018 ; Vol. 24. pp. 633-646.
@article{125e18ff636d4ec3897d7fdfba548509,
title = "Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the rhesus macaque",
abstract = "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.",
author = "Zeljka Smit-Mcbride and Johnny Nguyen and Elliott, {Garrett W.} and Zhe Wang and McBride, {Ryan A.} and Nguyen, {Anthony T.} and Oltjen, {Sharon L.} and Glenn Yiu and Thomasy, {Sara M.} and Pinkerton, {Kent E.} and Lee, {Eugene S.} and David Cunefare and Sina Farsiu and Morse, {Lawrence S.}",
year = "2018",
month = "9",
day = "24",
language = "English (US)",
volume = "24",
pages = "633--646",
journal = "Molecular Vision",
issn = "1090-0535",

}

TY - JOUR

T1 - Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the rhesus macaque

AU - Smit-Mcbride, Zeljka

AU - Nguyen, Johnny

AU - Elliott, Garrett W.

AU - Wang, Zhe

AU - McBride, Ryan A.

AU - Nguyen, Anthony T.

AU - Oltjen, Sharon L.

AU - Yiu, Glenn

AU - Thomasy, Sara M.

AU - Pinkerton, Kent E.

AU - Lee, Eugene S.

AU - Cunefare, David

AU - Farsiu, Sina

AU - Morse, Lawrence S.

PY - 2018/9/24

Y1 - 2018/9/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054452770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054452770&partnerID=8YFLogxK

M3 - Article

C2 - 30294202

AN - SCOPUS:85054452770

VL - 24

SP - 633

EP - 646

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -