Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their expression in the postnatal rat eye

Invest Ophthalmol Vis Sci. 1998 Jul;39(8):1399-409.

Abstract

Purpose: Transforming growth factor-beta has been shown to induce cataractous changes in rat lenses. This study assesses the relative cataractogenic potential of TGF-beta1, TGF-beta2, and TGF-beta3 and their expression patterns in the rat eye.

Methods: Lens epithelial explants and whole lenses from weanling rats were cultured with TGF-beta1, TGF-beta2, or TGF-beta3 at concentrations ranging from 0.025 ng/ml to 4 ng/ml for 3 to 5 days. Cataractous changes were monitored daily by phase contrast microscopy and by immunofluorescent detection of cataract markers alpha-smooth muscle actin and type I collagen. Expression of TGF-beta was studied by immunofluorescence and in situ hybridization on eye sections from neonatal and weanling rats.

Results: All three isoforms induced morphologic changes in lens epithelial explants and cultured lenses that are typically associated with human subcapsular cataract. Transforming growth factor-beta2 and TGF-beta3 were approximately 10 times more potent than TGF-beta1. All three isoforms were expressed in the eye in spatially distinct but overlapping patterns. Transforming growth factor-beta1 and TGF-beta2 and their mRNA were detected in most ocular tissues, including the lens. Although TGF-beta3 was immunolocalized in lens epithelium and fibers and in other ocular tissues, its mRNA was detected only in the retina and choroid.

Conclusions: All three isoforms of TGF-beta are potentially available to lens cells and have the potential to induce cataractous changes. The results suggest that TGF-beta activity is normally tightly regulated in the eye. Activation of TGF-beta in the lens environment, such as may occur during injury, in wound healing, or in pathologic conditions may contribute to cataractogenesis in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Cataract / chemically induced*
  • Cataract / metabolism
  • Cataract / pathology
  • Cells, Cultured
  • Collagen / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / pathology
  • Microscopy, Phase-Contrast
  • Organ Culture Techniques
  • RNA, Messenger / metabolism
  • Rats
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Actins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Collagen