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Wormstone, I. Michael 
ORCID: https://orcid.org/0000-0002-6423-7766, Tamiya, Shigeo, Anderson, Ian and Duncan, George
(2002)
TGF beta2 induced matrix modification and cell transdifferentiation in the human lens capsular bag.
Investigative Ophthalmology & Visual Science, 43 (7).
pp. 2301-2308.
ISSN 0146-0404
Abstract
purpose. To study the role of TGF-β2 in posterior capsule opacification (PCO) and to determine whether CAT-152 (lerdelimumab), a fully human monoclonal antibody that neutralizes the effect of TGF-β2, can also provide therapeutic benefit for PCO. methods. In vitro capsular bags were prepared from human donor eyes and maintained in a 5% CO2 atmosphere at 35°C. To investigate expression of active TGF-β2, capsular bags were incubated in serum-free EMEM for 2, 28, or more than 100 days and analyzed by ELISA (n ≥ 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-β2 with or without 10 μg/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-β2, matrix wrinkling, and expression of transdifferentiation markers αSMA 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-β2 (1–10 ng/mL) stimulated transdifferentiation and contraction of the capsular bag, resulting in light scatter. TGF-β2 also induced sustained release of MMP-2 and -9. Active TGF-β2 was detected in these cultures. The human monoclonal anti-TGF-β2 antibody CAT-152 (10 μg/mL) effectively inhibited all TGF-β2–induced effects. conclusions. Addition of TGF-β2 accelerates transdifferentiation and contraction of the capsular bag, resulting in light scatter. CAT-152 inhibited all the effects of TGF-β2 that were examined and therefore has the potential to suppress development of PCO and provide potential therapeutic benefit to cataract patients.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | Vishal Gautam |
| Date Deposited: | 01 Jul 2002 |
| Last Modified: | 22 Apr 2023 03:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/18062 |
| DOI: |
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