DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy.

Diabetic retinopathy, a microvascular complication of diabetes, is the leading cause of blindness in adults, but the molecular mechanism of its development remains unclear. Retinal mitochondrial DNA is damaged and hypermethylated, and mtDNA-encoded genes are downregulated. Expression of a long noncoding RNA (larger than 200 nucleotides, which does not translate into proteins), encoded by mtDNA, cytochrome B (Lnc), is also downregulated.

Long noncoding RNAs and metabolic memory associated with continued progression of diabetic retinopathy.

Progression of diabetic retinopathy resists arrest even after institution of intensive glycemic control, suggesting a "metabolic memory" phenomenon, but the mechanism responsible for this phenomenon is still elusive. Gene expression and biological processes can also be regulated by long noncoding RNAs (LncRNAs), the RNAs with >200 nucleotides and no open reading frame for translation, and several LncRNAs are aberrantly expressed in diabetes. Our aim was to identify retinal LncRNAs that fail to reverse after termination of hyperglycemia.

Role of ferroptosis in mitochondrial damage in diabetic retinopathy.

Diabetic retinopathy is driven by oxidative stress-mitochondrial damage. Activation of ROS producing cytosolic NADPH oxidase 2 (Nox2) in diabetes precedes retinal mitochondrial damage, initiating a vicious cycle of free radicals. Elevated ROS levels peroxidize membrane lipids increasing damaging lipid peroxides (LPOs).

Mitochondrial Genome-Encoded Long Noncoding RNA (Lnc) and Mitochondrial Ribonucleases in Diabetic Retinopathy.

Aim: Hyperglycemia damages mitochondria and downregulates transcription of mtDNA-encoded genes and the long noncoding RNA Lnc, causing mitochondrial genomic instability. The genes encoded by mtDNA are transcribed as large polycistronic transcripts, and the 5' ends of precursor tRNAs are processed by mitochondrial-targeted ribonuclease P (MRPPs). Our aim was to investigate the role of MRPP1 in the downregulation of Lnc in diabetic retinopathy.

Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease.

Purpose: Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness.

Design: We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system.