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B. Kovacs, S. Lumayag, S. Xu; MicroRNAs in Early Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5603.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is one of the leading causes of blindness in adults. The molecular mechanisms of the pathogenesis of DR are still not fully understood, and currently there is no effective prevention or treatment for DR. microRNAs (miRNAs) are small, non-coding, regulatory RNAs, and represent a newly recognized level of gene expression regulation. To start to understand the roles of miRNAs in DR, we hypothesized that miRNAs whose expression levels change significantly in the neuroretina (NR) and retinal endothelial cells (RECs) during the development of DR may be involved in the pathogenesis of DR. To identify these differentially expressed miRNAs, we performed miRNA expression profiling in the NR and RECs of diabetic and normal control rats.
Diabetes was induced in young adult (300g) male Sprague-Dawley rats by a single i.p. injection of streptozotocin (STZ) (65 mg/kg body weight). Three months after the onset of diabetes, we harvested the NR and isolated RECs by Magnetic Cell Sorting (MACS) with beads conjugated with PECAM-1 endothelial cell marker. TaqMan MicroRNA Arrays (Applied Biosystems) with full coverage of all known rodent miRNAs were used for miRNA profiling.
Our result showed that 1) 357 and 358 miRNAs were expressed in the control or DR NRs, including previously identified retina-specific miRNAs; 2) 222 and 217 miRNAs were expressed in control or DR RECs, respectively; 4) 87 miRNAs were differentially expressed (81 up- and 6 downregulated, p<0.01) in the NRs of DR rats compared to the controls; 5) 120 miRNAs were differentially expressed (16 up- and 104 downregulated, p<0.01) in RECs of DR rats compared to the controls. 6) Our functional annotation analysis on predicted targets of the differentially expressed miRNAs suggests that miRNAs may be involved in the pathogenesis of DR by modulating the expression of their downstream target genes, which are involved in the maintenance of the integrity of endothelial cells, inflammation, angiogenesis, cell cycle, apoptosis and oxidative stress pathways.
Our ongoing functional studies will further uncover the roles of these miRNAs in DR and their potentials as novel therapeutic targets for the prevention and/or treatment of DR.
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