Purchase this article with an account.
Sudha Priya Soundara Pandi, Mei Chen, Jasenka Guduric-Fuchs, David Simpson, Heping Xu; Age Alters MicroRNA Expression Profile in Mouse Retinal Pigment Epithelium (RPE)/choroid. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5132.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
MicroRNAs are non-coding regulatory RNAs, which fine tune and regulate gene expressions. The purpose of this study is to examine the influence of age on microRNA expression profile in retinal pigment epithelium (RPE)/choroid.
MicroRNAs were extracted from RPE/choroid of young (3-month) and adult (9-month) C57BL/6 mice, cDNA library construction using Illumina Truseq followed by Deep Sequencing using Illumina Genome Analyser. The data were annotated with miRBase using CLC Genomics Workbench V4.0. Each microRNA reads were normalised to number of microRNA reads/million mapped. Young and adult mice microRNA were compared and significant fold changes were calculated using Baggerley’s test. Age-related microRNA expression was identified using criteria of false discovery rate (FDR) < 0.05 in combination with fold change >2. The predicted target genes of significantly altered microRNAs and biological pathways that might be affected were analysed using DIANA miRPath database.
A total of 407 microRNAs were detected in RPE/choroid. Among them, 14 microRNAs (miR-21, -126, -30e, -16, -10a, -186, -199a, -145, -142, -195, -24, -15a, -335, -322) were downregulated and 2 microRNAs (miR486, miR423) upregulated in adult mice. Interestingly, 11 out of 14 downregulated microRNAs (miR-21, -126, -30e, -16, -10a, -186, -199a, -145, -142, -195, -15a) are known to negatively regulate upstream genes of various immune-related signalling pathways, including T/B cell receptor, NK cell mediated cytotoxicity, Toll-like-receptor, VEGF receptor, and cytokine receptor signalling pathways. In addition, 8 downregulated microRNAs (miR-21, -126, -30e, -16, -186, 199a, -145, -142) are known to negatively regulate upstream genes of leukocyte transendothelial migration pathway.
Our results show that age negatively regulates microRNA expression in RPE/choroid. Many of altered microRNAs can regulate the expression of genes involved in immune-related signalling pathways. Previously, we and others have observed increased inflammatory responses (e.g. immune cell infiltration and complement activation) at retinal-choroidal interface in aged mice. Our result suggests that down-regulation of miR-21, -126, -30e, -16, -10a, -186, -199a, -145, -142, -195, -15a may contribute to age-related para-inflammation at the RPE/choroid.
This PDF is available to Subscribers Only