Deficient activation and different expression of transforming growth factor-beta isoforms in active proliferative diabetic retinopathy and neovascular eye disease

Exp Clin Endocrinol Diabetes. 1999;107(1):21-8. doi: 10.1055/s-0029-1212068.


An increased expression and secretion of angiogenic growth factors was proposed to occur in proliferative diabetic retinopathy and other neovascularizing retinal diseases. However, a loss of anti-angiogenic factors also might promote retinal neovascularization. Therefore we investigated the active and latent vitreous levels of the subtypes of the endothelial anti-mitogen transforming growth factor-beta in vitreous of 58 patients. Four groups of patients were compared: Controls without retinal hypoxia, patients with quiescent and active proliferative diabetic retinopathy (PDR), and patients with severe retinal hypoxia resulting in rubeosis iridis. Whereas the amount of total TGF-beta in the four groups did not differ significantly, latent TGF-beta isoform expression showed complex alterations in ocular vitreous. Levels of active TGF-beta of patients with active PDR (79.5 +/- 28 pg/ml; n = 8) were decreased to 20% of the control levels (378 +/- 55 pg/ml; n = 12; p = 0.0005) and 25% of the mean concentration in quiescent PDR (346 +/- 64 pg/ml; n = 9; p = 0.0021). Levels in rubeosis (52 +/- 10 pg/ml; n = 10) did not differ significantly from those found in active PDR but were decreased to 15% of those in patients with quiescent PDR (p = 0.0004). Furthermore a highly significant inverse correlation between active TGF-beta and alpha2-antiplasmin, a liver produced inhibitor of the activation of TGF-beta by plasmin was noted (r = -0.59; n = 28; p = 0.001). We conclude that deficient activation of TGF-beta occurs in active proliferative diabetic retinopathy and in hypoxic angiogenesis most likely as a consequence of a blood retina barrier breakdown and influx of alpha2-antiplasmin from serum. The disinhibition of endothelial cell proliferation may be a central component in the process of neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetic Retinopathy / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Eye / blood supply*
  • Female
  • Fibrinolysin / metabolism
  • Fibrinolysin / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Retinal Diseases / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Vitreous Body / metabolism
  • alpha-Macroglobulins / metabolism


  • Transforming Growth Factor beta
  • alpha-Macroglobulins
  • plasmin-alpha(2)-macroglobulin complex
  • Fibrinolysin