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J. J. Chen, V. Eulo, Y. Huang, J. Rehman, S. M. Hariprasad, R. D. Jager, V. Sheth, D. L. Nicolae, Y. A. Lussier, M. A. Grassi; Study of Genetic Expression in Diabetic Retinopathy Reveals Unique Molecular Fingerprint. Invest. Ophthalmol. Vis. Sci. 2010;51(13):121.
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Previous studies exploring pathologic angiogenesis, the main blinding complication of diabetic retinopathy, implicated endothelial progenitor cells (EPCs) as contributors to neovascularization but never explored their role in the molecular basis of the disease. We sought to examine EPCs in patients with proliferative diabetic retinopathy for a unique transcriptional profile.
Human peripheral blood samples were collected from 9 control (diabetics without diabetic retinopathy) and 8* study patients (diabetics with active proliferative diabetic retinopathy) in the University of Chicago retina clinics. Between groups, patients did not differ significantly by age, gender, race, duration of diabetes, or glycemic index at last visit (p>.05). EPCs were isolated by flow cytometry, mRNA was run on Agilent 4x44k microarrays and results were processed by Bioconductor "Limma" package for background correction and "quantile" normalization, with differentially expressed genes identified using the Bioconductor "RankProd" package with false discovery rate < 10%.[*One study patient was excluded from the analysis due to inadequate RNA concentration at extraction.]
In order to reveal the critical biological pathways dysregulated in proliferative diabetic retinopathy, our study used a systems based genomics approach to uncover possible candidate genes by integrating gene expression profiling and bioinformatic analysis. 27 genes were found to show significant differential expression between groups (p<.001) with a mean fold change of 1.9 (range 1.1 to 4.6). Additionally, Heat Map cluster analysis resulted in fairly distinct separation between groups, indicating the presence of detectable differences in the pattern of gene expression.
Our study defines a set of genes which constitute a unique molecular fingerprint for proliferative diabetic retinopathy. Significant overlap exists between our gene set and profiles seen in other angiogenic conditions. Using a functional genomics approach, further studies are required to integrate genetic and expression findings to better define a molecular network for pathologic retinal angiogenesis.
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