Mitochondrial Fragmentation and Long Noncoding RNA in Diabetic Retinopathy.

Mitochondria are dynamic in nature and depending on the energy demand they fuse and divide. This fusion-fission process is impaired in diabetic retinopathy and the promoter DNA of , a fusion gene, is hypermethylated and its expression is downregulated. Long noncoding RNAs (RNAs with >200 nucleotides that do not encode proteins) can regulate gene expression by interacting with DNA, RNA, and proteins. Several LncRNAs are aberrantly expressed in diabetes, and among them, is upregulated in the retina, altering the expression of the genes associated with inflammation. Our aim was to investigate 's role in mitochondrial dynamics in diabetic retinopathy. Using -siRNA-transfected human retinal endothelial cells (HRECs) and human retinal Muller cells (RMCs) incubated in 20 mM D-glucose, Mfn2 expression and activity and its promoter DNA methylation were quantified. Mitochondrial integrity was evaluated by analyzing their fragmentation, ultrastructure, membrane potential, and oxygen consumption rate. Compared to normal glucose, high glucose upregulated expression and downregulated Mfn2 expression and activity in both HRECs and RMCs. -siRNA ameliorated the glucose-induced increase in promoter DNA hypermethylation and its activity. -siRNA also protected against mitochondrial fragmentation, structural damage, and reductions in the oxygen consumption rate. In conclusion, the upregulation of in diabetes facilitates promoter DNA hypermethylation in retinal vascular and nonvascular cells, leading to its suppression and the accumulation of the fragmented/damaged mitochondria. Thus, the regulation of has the potential to protect mitochondria and provide a possible new target to inhibit/prevent the blinding disease in diabetic patients.