Glucose-mediated regulation of transforming growth factor-beta (TGF-beta) and TGF-beta receptors in human retinal endothelial cells

Curr Eye Res. 1999 Aug;19(2):162-70. doi: 10.1076/ceyr.


Purpose: Diabetic retinopathy is a micro-angiopathy affecting predominantly small vessels of the retina. Clinical trials have demonstrated a strong association between tight glucose control and a reduction in the incidence and the severity of diabetic retinopathy. Transforming growth factor beta (TGF-beta) is involved in the control of endothelial cell proliferation, adhesion, and deposition of extracellular matrix, thus TGF-beta may play a role in the control of endothelial cell proliferation seen in the disease. We wished to investigate the regulation of transforming growth factor beta and its receptors (type I and II) in human retinal endothelial cells exposed to a range of glucose concentrations.

Methods: Human retinal endothelial cells were isolated from donor eyes, cultured in vitro and exposed to a range of glucose concentrations (0-25 mmol/l). TGF-beta protein and mRNA levels were determined by ELISA and Northern analysis, respectively. The binding affinities and TGF-beta receptor numbers were defined using a binding assay.

Results: Northern hybridisation and ELISA showed that after 8 hours, the level of TGF-beta mRNA and protein was significantly higher at 15mmol/l compared to 5, 20 or 25mmol/ l. Binding assays showed that for high glucose (25 mmol/l), human retinal endothelial cells express a population of TGF-beta receptors with higher affinity for its ligand than at 5 or 15 mmol/l.

Conclusions: These results demonstrate that glucose regulates TGF-beta mRNA and protein production and also TGF-beta receptor expression in human retinal endothelial cells. Thus, the glucose-mediated changes that occur in diabetic patients may expose human retinal endothelial cells to potential angiogenic factors which may influence disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Glucose / pharmacology*
  • Humans
  • RNA, Messenger / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Retinal Vessels / cytology
  • Retinal Vessels / drug effects
  • Retinal Vessels / metabolism*
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics


  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Glucose