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Abstract #15263 Published in IGR 8-4
Short-term exposure to transforming growth factor β induces long-term fibrotic responses
Wormstone IM; Anderson IK; Eldred JA; Dawes LJ; Duncan GExperimental Eye Research 2006; 83: 1238-1245
Transforming growth factor β (TGFβ), a potent inducer of cell transdifferentiation, is heavily implicated in fibrotic disorders. Following cataract surgery, aberrant cell growth across the collagenous matrix of the lens capsule leads to fibrosis, and in turn secondary visual loss, known as posterior capsule opacification (PCO). These modifications are associated with transdifferentiated cells. Following surgery, protein levels in the eye transiently increase, lasting a matter of days whereas PCO takes much longer to reach clinical significance. In the present study, a human lens culture model was employed to show that a relatively brief 2-day exposure to TGFβ gives rise to persistent, long-term signalling events resulting 28 days later in matrix contraction and transdifferentiation. These events can be suppressed by application of the human monoclonal anti-TGFβ2 antibody CAT-152 either simultaneously or after TGFβ2 exposure. Radiolabel binding studies revealed the lens capsule serves as a store for TGFβ2. Importantly, similar binding studies showed that the capsule could also serve as a reservoir for CAT-152. The data reveal the longevity of TGFβ2 action through matrix association, but also demonstrate how early application of a TGFβ2 antibody can overcome the detrimental TGFβ actions leading to potential inhibition of PCO development and other fibrotic disorders.
Dr. I.M. Wormstone, School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. i.m.wormstone@uea.ac.uk
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)