TGF-beta2-induced matrix modification and cell transdifferentiation in the human lens capsular bag

Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2301-8.


Purpose: To study the role of TGF-beta2 in posterior capsule opacification (PCO) and to determine whether CAT-152 (lerdelimumab), a fully human monoclonal antibody that neutralizes the effect of TGF-beta2, can also provide therapeutic benefit for PCO.

Methods: In vitro capsular bags were prepared from human donor eyes and maintained in a 5% CO(2) atmosphere at 35 degrees C. To investigate expression of active TGF-beta2, capsular bags were incubated in serum-free EMEM for 2, 28, or more than 100 days and analyzed by ELISA (n > or = 4 at each time point). To study underlying mechanisms, match-pair experiments were also performed, so that the medium was supplemented with 0, 1 or 10 ng/mL TGF-beta2 with or without 10 microg/mL CAT-152 (n = 4 in all cases). On-going observations were by phase-contrast microscopy. In addition, donor material from patients who had undergone cataract surgery was analyzed. Cellular architecture was examined by fluorescence cytochemistry. Expression of matrix metalloproteinase (MMP)-2 and -9 was assessed by gelatin zymography.

Results: Analysis of capsular bags from donor eyes that had received an intraocular lens (IOL) revealed the presence of endogenous active TGF-beta2, matrix wrinkling, and expression of transdifferentiation markers alphaSMA and fibronectin. When cultured in vitro, donor bags also showed sustained release of MMP-2 and -9. Culture of capsular bags prepared in vitro from whole lenses showed that TGF-beta2 (1-10 ng/mL) stimulated transdifferentiation and contraction of the capsular bag, resulting in light scatter. TGF-beta2 also induced sustained release of MMP-2 and -9. Active TGF-beta2 was detected in these cultures. The human monoclonal anti-TGF-beta2 antibody CAT-152 (10 microg/mL) effectively inhibited all TGF-beta2-induced effects.

Conclusions: Addition of TGF-beta2 accelerates transdifferentiation and contraction of the capsular bag, resulting in light scatter. CAT-152 inhibited all the effects of TGF-beta2 that were examined and therefore has the potential to suppress development of PCO and provide potential therapeutic benefit to cataract patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Cataract / etiology*
  • Cataract / metabolism
  • Cataract / pathology
  • Cataract / prevention & control
  • Cataract Extraction
  • Cell Differentiation / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / metabolism*
  • Fibronectins / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Lens Capsule, Crystalline / drug effects*
  • Lens Capsule, Crystalline / metabolism
  • Lens Capsule, Crystalline / pathology
  • Lens Implantation, Intraocular
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Organ Culture Techniques
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta2


  • Actins
  • Antibodies, Monoclonal
  • Fibronectins
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9