Afshan N Malik1, Chandani K Parsade2, Saima Ajaz2, Roxanne Crosby-Nwaobi3, Luigi Gnudi4, Anna Czajka2, Sobha Sivaprasad3. 1. 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. 2. King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK. 3. King's College London, Laser and Retinal Research Unit, Department of Ophthalmology, UK; King's College London, NIHR Moorfields Biomedical Research Centre, UK. 4. King's College London, Cardiovascular Division, Faculty of Life Science & Medicine, UK.
Abstract
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.
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.
Authors: Janine Aucamp; Abel J Bronkhorst; Dimetrie L Peters; Hayley C Van Dyk; Francois H Van der Westhuizen; Piet J Pretorius Journal: Cell Mol Life Sci Date: 2017-03-18 Impact factor: 9.261
Authors: Aldi T Kraja; Chunyu Liu; Jessica L Fetterman; Mariaelisa Graff; Christian Theil Have; Charles Gu; Lisa R Yanek; Mary F Feitosa; Dan E Arking; Daniel I Chasman; Kristin Young; Symen Ligthart; W David Hill; Stefan Weiss; Jian'an Luan; Franco Giulianini; Ruifang Li-Gao; Fernando P Hartwig; Shiow J Lin; Lihua Wang; Tom G Richardson; Jie Yao; Eliana P Fernandez; Mohsen Ghanbari; Mary K Wojczynski; Wen-Jane Lee; Maria Argos; Sebastian M Armasu; Ruteja A Barve; Kathleen A Ryan; Ping An; Thomas J Baranski; Suzette J Bielinski; Donald W Bowden; Ulrich Broeckel; Kaare Christensen; Audrey Y Chu; Janie Corley; Simon R Cox; Andre G Uitterlinden; Fernando Rivadeneira; Cheryl D Cropp; E Warwick Daw; Diana van Heemst; Lisa de Las Fuentes; He Gao; Ioanna Tzoulaki; Tarunveer S Ahluwalia; Renée de Mutsert; Leslie S Emery; A Mesut Erzurumluoglu; James A Perry; Mao Fu; Nita G Forouhi; Zhenglong Gu; Yang Hai; Sarah E Harris; Gibran Hemani; Steven C Hunt; Marguerite R Irvin; Anna E Jonsson; Anne E Justice; Nicola D Kerrison; Nicholas B Larson; Keng-Hung Lin; Latisha D Love-Gregory; Rasika A Mathias; Joseph H Lee; Matthias Nauck; Raymond Noordam; Ken K Ong; James Pankow; Amit Patki; Alison Pattie; Astrid Petersmann; Qibin Qi; Rasmus Ribel-Madsen; Rebecca Rohde; Kevin Sandow; Theresia M Schnurr; Tamar Sofer; John M Starr; Adele M Taylor; Alexander Teumer; Nicholas J Timpson; Hugoline G de Haan; Yujie Wang; Peter E Weeke; Christine Williams; Hongsheng Wu; Wei Yang; Donglin Zeng; Daniel R Witte; Bruce S Weir; Nicholas J Wareham; Henrik Vestergaard; Stephen T Turner; Christian Torp-Pedersen; Evie Stergiakouli; Wayne Huey-Herng Sheu; Frits R Rosendaal; M Arfan Ikram; Oscar H Franco; Paul M Ridker; Thomas T Perls; Oluf Pedersen; Ellen A Nohr; Anne B Newman; Allan Linneberg; Claudia Langenberg; Tuomas O Kilpeläinen; Sharon L R Kardia; Marit E Jørgensen; Torben Jørgensen; Thorkild I A Sørensen; Georg Homuth; Torben Hansen; Mark O Goodarzi; Ian J Deary; Cramer Christensen; Yii-Der Ida Chen; Aravinda Chakravarti; Ivan Brandslund; Klaus Bonnelykke; Kent D Taylor; James G Wilson; Santiago Rodriguez; Gail Davies; Bernardo L Horta; Bharat Thyagarajan; D C Rao; Niels Grarup; Victor G Davila-Roman; Gavin Hudson; Xiuqing Guo; Donna K Arnett; Caroline Hayward; Dhananjay Vaidya; Dennis O Mook-Kanamori; Hemant K Tiwari; Daniel Levy; Ruth J F Loos; Abbas Dehghan; Paul Elliott; Afshan N Malik; Robert A Scott; Diane M Becker; Mariza de Andrade; Michael A Province; James B Meigs; Jerome I Rotter; Kari E North Journal: Am J Hum Genet Date: 2018-12-27 Impact factor: 11.025