Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy

Aims: We previously showed that circulating mitochondrial DNA (MtDNA) levels are altered in diabetic nephropathy. The aim of the current study was to determine if circulating MtDNA levels are altered in patients with diabetic retinopathy. 

Methods: Patients with diabetes (n = 220) were studied in a clinical setting using a cross-sectional study design as the following groups: DR-0 (no retinopathy, n = 53), DR-m (mild non-proliferative diabetic retinopathy NPDR, n = 98) and DR-s (severe proliferative diabetic retinopathy, n = 69). MtDNA content in peripheral blood DNA was measured as the mitochondrial to nuclear genome ratio using real time qPCR. Circulating cytokines were measured using the luminex assay and MtDNA damage was assessed using PCR. Differences were considered significant at P <. 0.05. 

Results: Circulating MtDNA values were higher in DR-m compared to DR-0 (P = 0.02) and decreased in DR-s compared to DR-m (P = 0.001). These changes remained significant after adjusting for associated parameters. In parallel there were increased levels of circulating cytokines IL-4 (P = 0.005) and TNF-α (P = 0.02) in the DR-s group and increased MtDNA damage in DR-m patients compared to DR-0 (P = 0.03). 

Conclusions: Our data show that circulating MtDNA levels are independently associated with diabetic retinopathy, showing an increase in DR-m and decrease in DR-s with a parallel increase in MtDNA damage and inflammation. Hyperglycemia-induced changes in MtDNA in early diabetes may contribute to inflammation and progression of diabetic retinopathy. Longitudinal studies should be carried out to determine a potential causality of MtDNA in diabetic retinopathy.