Expression Profiling Analysis Reveals Key MicroRNA–mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa

Abstract

PurposeThe aim of this study was to identify differentially expressed microRNAs (miRNAs) that might play an important role in the etiology of retinal degeneration in a genetic mouse model of retinitis pigmentosa (rd10 mice) at initial stages of the disease.MethodsmiRNAs–mRNA interaction networks were generated for analysis of biological pathways involved in retinal degeneration.ResultsOf more than 1900 miRNAs analyzed, we selected 19 miRNAs on the basis of (1) a significant differential expression in rd10 retinas compared with control samples and (2) an inverse expression relationship with predicted mRNA targets involved in biological pathways relevant to retinal biology and/or degeneration. Seven of the selected miRNAs have been associated with retinal dystrophies, whereas, to our knowledge, nine have not been previously linked to any disease.ConclusionsThis study contributes to our understanding of the etiology and progression of retinal degeneration.

Bioinformatics Analysis of Weighted Genes in Diabetic Retinopathy

“…Huang et al 26 demonstrated that miR-155 expression is more than five-fold greater in kidney samples from diabetic nephropathy patients than in those from controls and that miR-155 expression gradually increases during disease induction and progression in rat models of type 1 and type 2 diabetic nephropathy. Loscher et al 27 and Anasagasti et al 28 reported that miR-1a was upregulated in mouse models. In addition, miR-122 is a highly abundant, hepatocyte-specific miRNA, and miR-122 affects lipid metabolism in the liver.…”

Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa

“…Only those genes that showed, concomitantly, (1) differential expression levels between treated and control groups (scramble and injection controls) and (2) no differences between scramble and injection controls, were considered for further analysis. The selected genes were subjected to genetic ontology (GO), biological pathway enrichment analysis, and miRNA-mRNA interaction network studies, following the same procedure detailed in [ 30 ]. We analyzed the relative miRNA expression within photoreceptor cells compared to the rest of the retina in a selection of seven miRNAs ( Figure S2 ).…”

“…For this, we used RT-qPCR (miScript Primer Assays and miScript SYBR Green PCR Kit from Qiagen, Hilden, Germany). Each biological sample was amplified in triplicate as previously described [ 30 ].…”

“…Expression levels of differentially expressed mRNAs were validated by quantitative PCR (RT-qPCR), following previously reported methods with minor modifications [ 30 ]. Briefly, RT-qPCR was done using miScript Primer Assays and SYBR Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA).…”

“…More recently, using an in vitro model of RP, Donato and colleagues found 23 grouped miRNAs with altered expression in human RPE cells under oxidative stress conditions [ 29 ]. Additionally, we have recently found a group of differentially expressed miRNAs in the widely accepted rd10 mouse model of RP [ 30 ].…”