IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2003;44:2163-2170.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0662
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Noda, K.
Right arrow Articles by Ikeda, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Noda, K.
Right arrow Articles by Ikeda, E.

Production and Activation of Matrix Metalloproteinase-2 in Proliferative Diabetic Retinopathy

Kousuke Noda,1,2 Susumu Ishida,1,2 Makoto Inoue,2 Ken-ichi Obata,3 Yoshihisa Oguchi,2 Yasunori Okada,1 and Eiji Ikeda1

1From the Departments of Pathology and 2Ophthalmology, Keio University School of Medicine, and 3Daiichi Fine Chemical Co., Toyama, Japan.

PURPOSE. To investigate the matrix metalloproteinase (MMP) species and their activation associated with the pathogenesis of proliferative diabetic retinopathy (PDR).

METHODS. Sandwich enzyme immunoassays were used to measure concentrations of MMP-1, -2, -3, -7, -8, -9, and -13 in vitreous samples from patients with PDR and nondiabetic vitreoretinal diseases. To evaluate activation ratios of the zymogen of MMP-2 (proMMP-2) and -9 (proMMP-9) in the vitreous samples and fibrovascular tissues, gelatin zymography was performed. Production and tissue localization of MMP-2, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP)-2, and MMP-9 in the fibrovascular tissues were examined by immunohistochemistry. mRNA expression of MT1-MMP in the tissues was determined by reverse transcription–polymerase chain reaction (RT-PCR).

RESULTS. Among the seven different MMPs examined in the vitreous samples, only the levels of MMP-2 and -9 were significantly higher in the PDR samples than in the control. However, activation ratios of proMMP-2 (10.6% ± 11.8%) and proMMP-9 (2.5% ± 5.1%) in PDR vitreous samples were low and not significantly different from those of the control. In contrast, high activation ratios of proMMP-2 (54.3% ± 13.6%) and notable activation of proMMP-9 (19.5% ± 7.8%) were observed in the fibrovascular tissues. Immunohistochemical study demonstrated the localization of MMP-2 and -9 in the endothelial cells and glial cells of the fibrovascular tissues. MMP-2 was colocalized with MT1-MMP and TIMP-2, which are an activator and an activation-enhancing factor, respectively, for proMMP-2. RT-PCR analysis indicated the gene expression of MT1-MMP in the tissues.

CONCLUSIONS. These data demonstrate that proMMP-2 is efficiently activated in the fibrovascular tissues of PDR, probably through interaction with MT1-MMP and TIMP-2, and suggest the possibility that the activity of MMP-2 and MT1-MMP is involved in the formation of the fibrovascular tissues.




This article has been cited by other articles:


Home page
 DiabetesHome page
U. Hiden, E. Glitzner, M. Ivanisevic, J. Djelmis, C. Wadsack, U. Lang, and G. Desoye
MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-{alpha} Levels
Diabetes, January 1, 2008; 57(1): 150 - 157.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Hollborn, C. Stathopoulos, A. Steffen, P. Wiedemann, L. Kohen, and A. Bringmann
Positive Feedback Regulation between MMP-9 and VEGF in Human RPE Cells
Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4360 - 4367.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
K. M. Thrailkill, R. C. Bunn, C. S. Moreau, G. E. Cockrell, P. M. Simpson, H. N. Coleman, J. P. Frindik, S. F. Kemp, and J. L. Fowlkes
Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes
Diabetes Care, September 1, 2007; 30(9): 2321 - 2326.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. Koto, K. Takubo, S. Ishida, H. Shinoda, M. Inoue, K. Tsubota, Y. Okada, and E. Ikeda
Hypoxia Disrupts the Barrier Function of Neural Blood Vessels through Changes in the Expression of Claudin-5 in Endothelial Cells
Am. J. Pathol., April 1, 2007; 170(4): 1389 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
S. G. Shaw, J. P. Boden, E. Biecker, J. Reichen, and B. Rothen
Endothelin Antagonism Prevents Diabetic Retinopathy in NOD Mice: A Potential Role of the Angiogenic Factor Adrenomedullin.
Experimental Biology and Medicine, June 1, 2006; 231(6): 1101 - 1105.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. Noda, S. Ishida, H. Shinoda, T. Koto, T. Aoki, K. Tsubota, Y. Oguchi, Y. Okada, and E. Ikeda
Hypoxia Induces the Expression of Membrane-Type 1 Matrix Metalloproteinase in Retinal Glial Cells
Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3817 - 3824.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Notari, A. Miller, A. Martinez, J. Amaral, M. Ju, G. Robinson, L. E. H. Smith, and S. P. Becerra
Pigment Epithelium-Derived Factor Is a Substrate for Matrix Metalloproteinase Type 2 and Type 9: Implications for Downregulation in Hypoxia
Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2736 - 2747.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the Association for Research in Vision and Ophthalmology