Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice

Biochem Biophys Res Commun. 2008 Feb 15;366(3):814-20. doi: 10.1016/j.bbrc.2007.12.041. Epub 2007 Dec 18.


We previously proposed that hyperglycemia-induced mitochondrial ROS overproduction is a key event in the development of diabetic complications. In this study, we established a novel transgenic mouse (eMnSOD-Tg), which specifically expressed MnSOD in endothelial cells, by employing a Tie2 promoter/enhancer, and investigated the impact of mitochondrial ROS production on diabetic retinopathy in vivo. Using immunohistochemistry, overexpression of MnSOD in endothelial cells was confirmed in eMnSOD-Tg mice. By introduction of diabetes by streptozotocin, levels of urinary 8-hydroxydeoxyguanosine, a marker of mitochondrial oxidative stress, and expression of VEGF mRNA and protein and fibronectin mRNA in retinas were increased in wild-type littermates. However, these observations were ameliorated in eMnSOD-Tg mice, although control and eMnSOD-Tg mice showed a comparable level of hyperglycemia. In the present study, we newly developed a line of transgenic mice, which specifically express MnSOD in endothelium. In addition, overexpression of mitochondrial-specific SOD in endothelium could prevent diabetic retinopathy in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetic Retinopathy / chemically induced
  • Diabetic Retinopathy / metabolism*
  • Endothelial Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Reactive Oxygen Species / metabolism*
  • Retina / metabolism*
  • Streptozocin
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*


  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • Streptozocin
  • Superoxide Dismutase