Exacerbation of TGF-beta-induced cataract by FGF-2 in cultured rat lenses

Mol Vis. 2003 Dec 15:9:689-700.

Abstract

Purpose: Culturing rat lenses with transforming growth factor-beta (TGFbeta) results in the formation of anterior, opaque subcapsular plaques which exhibit many of the features of human subcapsular cataract. The present study was undertaken to determine whether this process is influenced by the presence of fibroblast growth factor (FGF), a normal component of the lens environment in situ.

Methods: Rat lenses were cultured for 4-8 days with TGFbeta-2, alone or in combination with FGF-2, PDGF-AA, or the growth factor inhibitors poly(4-styrenesulfonic acid) (PSS) and suramin. Responses were assessed by monitoring opacification, by routine histology and immunolocalization of markers for fibrotic change (a-smooth muscle actin, fibronectin, and type I collagen), or by measuring DNA accumulation in the epithelial region.

Results: Supplementing TGFbeta at a barely cataractogenic dose with 2.5-30 ng/ml FGF-2 resulted in a very strong opacification response. The exceptionally large plaques that formed were similar histologically to those induced by TGFbeta alone at higher concentrations and showed immunoreactivity for all markers. PDGF at a concentration equivalent to FGF in terms of proliferative potential did not demonstrate this effect. Addition of either PSS or suramin reduced the opacification response induced by a cataractogenic dose of TGFbeta alone.

Conclusions: FGF has been identified as a factor capable of exacerbating the cataractogenic effects of TGFbeta. Thus FGF inhibitors, as well as TGFbeta inhibitors, have the potential to protect the lens against TGFbeta-induced cataractous changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Cataract / chemically induced*
  • Cataract / metabolism
  • Cataract / pathology
  • Collagen Type I / metabolism
  • DNA / biosynthesis
  • Drug Combinations
  • Drug Synergism
  • Female
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibronectins / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / ultrastructure
  • Organ Culture Techniques
  • Platelet-Derived Growth Factor / pharmacology
  • Polymers / pharmacology
  • Rats
  • Rats, Wistar
  • Sulfonic Acids / pharmacology
  • Suramin / pharmacology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta2

Substances

  • Actins
  • Collagen Type I
  • Drug Combinations
  • Fibronectins
  • Platelet-Derived Growth Factor
  • Polymers
  • Sulfonic Acids
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • platelet-derived growth factor A
  • Fibroblast Growth Factor 2
  • Suramin
  • DNA
  • styrenesulfonic acid polymer