King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK.
King's College London, Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, UK.
Diabetes Res Clin Pract. 2015 Dec;110(3):257-65. doi: 10.1016/j.diabres.2015.10.006. Epub 2015 Oct 22.
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.
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.
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).
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.
我们之前的研究表明，循环线粒体 DNA（MtDNA）水平在糖尿病肾病中发生改变。本研究旨在确定糖尿病视网膜病变患者的循环 MtDNA 水平是否发生改变。
采用横断面研究设计，在临床环境中研究了 220 例糖尿病患者，分为以下组：DR-0（无视网膜病变，n=53）、DR-m（轻度非增生性糖尿病视网膜病变 NPDR，n=98）和 DR-s（严重增生性糖尿病视网膜病变，n=69）。使用实时 qPCR 以线粒体与核基因组的比值来测量外周血 DNA 中的 MtDNA 含量。使用 Luminex assay 测量循环细胞因子，使用 PCR 评估 MtDNA 损伤。差异有统计学意义（P<0.05）。
与 DR-0 相比，DR-m 患者的循环 MtDNA 值更高（P=0.02），与 DR-m 相比，DR-s 患者的循环 MtDNA 值更低（P=0.001）。调整相关参数后，这些变化仍然具有统计学意义。与此同时，DR-s 组的循环细胞因子 IL-4（P=0.005）和 TNF-α（P=0.02）水平升高，与 DR-0 相比，DR-m 患者的 MtDNA 损伤增加（P=0.03）。
我们的数据表明，循环 MtDNA 水平与糖尿病视网膜病变独立相关，DR-m 患者的循环 MtDNA 水平升高，DR-s 患者的循环 MtDNA 水平降低，同时伴有 MtDNA 损伤和炎症的增加。早期糖尿病中由高血糖引起的 MtDNA 变化可能导致炎症和糖尿病视网膜病变的进展。应进行纵向研究以确定 MtDNA 在糖尿病视网膜病变中的潜在因果关系。
