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      Transcript Expression of Matrix Metalloproteinases in the Conjunctiva following Glaucoma Filtration Surgery in Rabbits

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          Abstract

          Purpose: To determine the changes in the expression of transcripts of matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMP) in the conjunctiva following glaucoma filtration surgery (GFS). Methods: The reverse transcription-polymerase chain reaction method was performed on tissue specimens obtained from adult rabbits undergoing GFS at various postoperative time points. Results: MMP 1 decreased more than 7-fold from its baseline level during the first 2 weeks following surgery. MMP 2 decreased on the 1st postoperative day, but increased on day 2, and remained elevated for 2 weeks. The postoperative level of MMP 14 did not change much from baseline except that noted on day 9. The TIMP 1 expression showed an early biphasic pattern. MMP 3 and MMP 9 were not detected in all the specimens. Conclusions: The transcript expression of MMPs and TIMP 1 in the conjunctiva is altered following GFS, with each gene product demonstrating a unique temporal pattern.

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          Most cited references 8

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          Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1-MMP and MMP-2 in microvascular endothelial cells.

          Matrix metalloproteinases (MMPs) are hypothesized to play a key role in the processes of endothelial cell migration and matrix remodeling during angiogenesis. We utilized an in vitro model of microvascular endothelial cell angiogenesis, cells cultured within a collagen matrix, to investigate the MMP profile of endothelial cells undergoing angiogenesis. We demonstrated by gelatin zymography that monolayer cultures (two-dimensional) of endothelial cells constitutively expressed low levels of latent MMP-2, but that culture in a three-dimensional collagen matrix increased the total amount of MMP-2 mRNA and protein. Furthermore, 51% of total MMP-2 protein was activated in the three-dimensional culture lysates, compared with 3.5% in two-dimensional culture. The mRNA and protein of MT1-MMP, the putative activator of MMP-2, were up-regulated in endothelial cells cultured in three-dimensional as compared with two-dimensional culture. Treatment of cultures with MMP inhibitors blocked activation of MMP-2 and inhibited formation of endothelial cell networks within the collagen gel. Induction of MT1-MMP and MMP-2 appeared to be specific to collagen, inasmuch as culture of the endothelial cells on top of, or within, a Matrigel(R) matrix neither increased total MMP-2 nor increased activation of MMP-2. These results suggest that MT1-MMP activation of MMP-2 occurs in endothelial cells undergoing angiogenesis, that this activation has a functional role in endothelial cell organization, and that specific matrix interactions may be critical for the increased expression of MT1-MMP and MMP-2.
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            Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery.

            To determine whether postoperative application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (ilomastat), reduces scarring after glaucoma filtration surgery. In a randomized, prospective, masked-observer study, 40 New Zealand White rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive postoperative subconjunctival injections of either phosphate-buffered saline (PBS) or 100 microM ilomastat for 10 days. The animals were killed on days 7, 14, 21, and 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (alphaSMA) and extracellular matrix components in the two groups. Surgical outcome was significantly prolonged in the ilomastat-treated group compared with the vehicle-treated group (P < 0.001). At day 30, all the blebs had survived except two in the ilomastat-treated group, whereas no blebs survived to day 30 with vehicle treatment (n = 11). The intraocular pressure remained significantly lower throughout the course of the experiment in the ilomastat group compared with the vehicle group (P < 0.0017). Histologically, less scar tissue was observed at the sclerostomy site with inhibition of MMP, compared with vehicle treatment. The data presented suggest that the healing response after surgery can be modulated by inhibiting the effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.
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              MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology

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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2004
                April 2004
                17 March 2004
                : 36
                : 2
                : 114-119
                Affiliations
                aDepartment of Ophthalmology, Taipei Veterans General Hospital and bNational Yang-Ming University School of Medicine, Taipei, cDepartment of Medical Research, Chi Mei Medical Center, Tainan, and dDepartment of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainen, Taiwan
                Article
                76891 Ophthalmic Res 2004;36:114–119
                10.1159/000076891
                15017108
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 1, References: 29, Pages: 6
                Categories
                Original Paper

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