The Detection and Partial Localisation of Heteroplasmic Mutations in the Mitochondrial Genome of Patients with Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is a common complication of diabetes and a major cause of acquired blindness in adults. Mitochondria are cellular organelles involved in energy production which contain mitochondrial DNA (mtDNA). We previously showed that levels of circulating mtDNA were dysregulated in DR patients, and there was some evidence of mtDNA damage. In the current project, our aim was to confirm the presence of, and determine the location and prevalence of, mtDNA mutation in DR. DNA isolated from peripheral blood from diabetes patients (n = 59) with and without DR was used to amplify specific mtDNA regions which were digested with surveyor nuclease S1 to determine the presence and location of heteroplasmic mtDNA mutations were present. An initial screen of the entire mtDNA genome of 6 DR patients detected a higher prevalence of mutations in amplicon P, covering nucleotides 14,443 to 1066 and spanning the control region. Further analysis of 42 subjects showed the presence of putative mutations in amplicon P in 36% (14/39) of DR subjects and in 10% (2/20) non-DR subjects. The prevalence of mutations in DR was not related to the severity of the disease. The detection of a high-prevalence of putative mtDNA mutations within a specific region of the mitochondrial genome supports the view that mtDNA damage contributes to DR. The exact location and functional impact of these mutations remains to be determined.

mtDNA and Mitochondrial Stress Signaling in Human Diseases: A Special Issue

“…A paper showed the higher prevalence of heteroplasmic mtDNA mutations, mostly localized in the so-called control region, in diabetes patients affected by diabetic retinopathy (DR). The sequential suggestion that mtDNA damage might contribute to the onset of DR and might represent a potential therapeutic target through strategies for the removal of mutated circulating molecules completed this interesting work by Malik et al [9]. As for neurodegenerative diseases associated with mitochondrial oxidative stress, a paper dealt with a C. elegans model of Parkinson's disease (PD), highlighting the relevance of environmental interactions with genetic deficiencies [10], and another focused on the possible use of mitochondrion-derived vesicles as early biomarkers of PD [11].…”