Effects of aging and chronic cigarette exposure on ocular circulatory microRNAs in the Rhesus macaque

ABSTRACT: Purpose: The purpose of this study was to identify cigarette smoke (CS) induced changes in circulatory microRNA (miRNA) in the plasma and ocular fluids of the Rhesus macaque and compare them to normal age-related changes, with the ultimate goal to develop an animal model of early dry age-related macular degeneration (AMD). AMD is a blinding disease having both genetic and environmental components, with cigarette smoke exposure (CS) as the leading environmental risk factor. Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC) at UC Davis. We used 6 animals of the same gender per group: Group 1 (young, 2-4 years old), Group 2 (old, 20-25 years old), Group 3 (middle aged, 9-12 years old) and Group 4 (9-12 years old, exposed to smoke for 1 month). Group 4 macaques were clinically assessed prior to and following CS exposure. Ocular fluids and plasma samples were collected, miRNA isolated, and expression data obtained from Affymetrix miRNA GeneTitan Array Plates 4.0, followed by bioinformatics analysis on Affymetrix Expression Console (EC) and Transcriptome Analysis Software (TAS), and using ANOVA. Results: Statistically significant changes were seen in miRNA populations in ocular fluids and plasma. In the plasma samples, 45 miRNAs were strongly upregulated (Fold Change >+/-1.5, p<0.05) upon CS exposure, while in aging monkeys different miRNAs in plasma were affected, and downregulated. In the vitreous, 3 miRNAs were downregulated in animals exposed to CS, intriguing enough two of them (miR-6794 and miR-6790) were the same ones downregulated with age. Retinal imaging using OCT did not show any significant changes in retinal thickness. Cotinine assays showed that animals received on average dose of 50-60 ng/ml cotinine, a marker for significant CS exposure. Conclusions: One month of CS exposure of Rhesus macaques resulted in significant changes of expression of circulatory miRNAs. We identified several CS related miRNA changes that are plasma or ocular fluid-specific. Healthy aging changes of miRNAs populations were different from the CS exposure induced changes in plasma, while the ones in vitreous were similar. This data will be utilized to develop an animal model of early dry AMD, using a monkey model exposed to CS.

ORGANISM(S): synthetic construct Macaca mulatta

PROVIDER: GSE108951 | GEO | 2019/05/17

REPOSITORIES: GEO