title: Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy.
abstract: OBJECTIVE
  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.
authors.affiliation: King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK. Electronic address: afshan.malik@kcl.ac.uk.
authors.forename: Afshan N
authors.initials: AN
authors.lastname: Malik
authors.affiliation: King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK.
authors.forename: Chandani K
authors.initials: CK
authors.lastname: Parsade
authors.affiliation: King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK.
authors.forename: Saima
authors.initials: S
authors.lastname: Ajaz
authors.affiliation: King's College London, Laser and Retinal Research Unit, Department of Ophthalmology, UK; King's College London, NIHR Moorfields Biomedical Research Centre, UK.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Crosby-Nwaobi
authors.affiliation: King's College London, Cardiovascular Division, Faculty of Life Science & Medicine, UK.
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.affiliation: King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Czajka
authors.affiliation: King's College London, Laser and Retinal Research Unit, Department of Ophthalmology, UK; King's College London, NIHR Moorfields Biomedical Research Centre, UK.
authors.forename: Sobha
authors.initials: S
authors.lastname: Sivaprasad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D056915:DNA Copy Number Variations; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood* / Q000150:complications; D018450:Disease Progression; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007249:Inflammation / Q000097:blood* / Q000150:complications; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004272:DNA, Mitochondrial; C508598:IL4 protein, human; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4
keywords: Diabetic retinopathy; Inflammation; Mitochondrial DNA