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Kingsley Okafor, Zeljka Smit-McBride, Matthew Bordbari, Amar P Patel, Allan A Hunter, Lawrence S Morse; MicroRNA in vitreous humor as putative biomarkers of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4699.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy carries considerable morbidity for patients. MicroRNA’s are a newly discovered highly conserved class of RNA that post-transcriptionally regulates gene expression by degrading or translating mRNA. Our study aims to identify microRNAs (miRNA) as prognostic tools in diabetic patients for development of diabetic retinopathy.
Vitreous samples from 28 patients undergoing vitrectomy were collected. Group 1:Type I diabetics with retinopathy(n=4), Group 2:Type II diabetics with retinopathy(n=10), Group 3:Type II diabetics without retinopathy(n=4), and Group 4:Control patients undergoing vitrectomy without known diabetes(n=10). MiRNA were isolated with Exiqon RNA purification kit for human samples. Presence of miRNA was confirmed and quantified using a BioAnalyzer and small RNA chip. Samples were labeled with FlashTag procedure and hybridized to Affymetrix microRNA GeneChip to identify miRNA’s present. Normalization of the .cel files using RMA algorithm was performed using Affymetrix software Expression Console (EC), while for ANOVA and fold change analysis Transcriptome Analysis Console (TAC) was used. We identified significant changes (p<0.05), and fold change (FC) increases (FC >1.5) and decreases (FC <-1.5) of miRNA expression between sample groups and controls.
Diabetics with retinopathy (type I and II) showed significant (p<0.05) increases of miRNA-425 (FC=1.8/1.5 respectively). Diabetics with retinopathy (type I and II) also showed significant decreases of miR-20b (FC= -12.88/-9.32 respectively), miR-20a (FC= -2.69/-2.32 respectively), and miR-451 (FC= -5.21/-2.16 respectively). Type II diabetics without retinopathy showed significant elevation of miR-625 (FC=2.08) compared to controls.
There are unique differences in the miRNA profiles of vitreous humor in patients with proliferative diabetic retinopathy compared to controls. Furthermore, these miRNA biomarkers are unique when compared to diabetics without retinopathy. Current literature demonstrate that elevated miR-425 levels are found in models of metabolic syndrome, repressed levels of miR-20b can increase cell proliferation/adhesion in cancer models, and down-regulation of miR-451 can lead to diabetic cardiomyopathy. These findings may give greater insight into the pathophysiology underlying diabetic retinopathy, as well as help develop prognostic biomarkers and potential novel targets for furture therapies.
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