MMP inhibitors might be competitors to Trabio (preclinical):
Message 19066112
And a recent paper:
rcophth.ac.uk
12.10 p.m. Post-operative neutralisation of transforming growth factor Beta-2 can prevent long-term scarring after experimental glaucoma filtration surgery.
A. L. Mead, T. T. L. Wong, M. F. Cordeiro, I. K. Anderson, P. T. Khaw
Institute of Ophthalmology, London
Purpose: The healing response after glaucoma filtration surgery (GFS) is the major obstacle to long-term intraocular pressure control and arrest of glaucomatous progression. We investigated if prolonged post-operative application of CAT-152, a human antibody that neutralises Transforming Growth Factor-B2, could prevent scarring after GFS and compared its actions to the gold standard post-operative anti-scarring agent 5-fluorouracil (5-FU).
Methods: The effect of CAT-152 on TGF-B2 mediated collagen production and alpha smooth muscle actin expression from human cultures of conjunctival fibroblasts was determined. In a randomised, masked observer study, following modified GFS, 54 rabbits received a postoperative course of subconjunctival injections (100ul) of either CAT-152 (100ug) or 5-FU (5mg) or received no treatment. Bleb characteristics and reaction to treatment were assessed. Immunohistochemistry, electron microscopy and histological staining were performed to evaluate the mechanism of action of CAT-152 on the extracellular matrix changes.
Results: TGF-B2 caused a concentration-dependent increase in collagen production and ASMA expression in conjunctival fibroblasts, which was completely inhibited by CAT-152. In vivo, CAT-152 significantly improved surgical outcome (log rank p<0.001) and reduced subconjunctival collagen deposition (p<0.01) compared to 5-FU and control. CAT-152 treatment improved bleb morphology (p<0.05) and was well tolerated. 5-FU prolonged the duration of corneal epitheliopathy (p<0.01).
Conclusions: Post-operative CAT-152 improved surgical outcome and reduced the risk of corneal side effects compared to 5-FU. CAT-152 appears to act by inhibition of TGF-B2 induced collagen production and myofibroblast mediated contraction. Post-operative CAT-152 may provide a novel, safer approach to the prevention of late surgical failure after GFS and maintenance of long-term intraocular pressure control... |
