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


     

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 Majka, S.
Right arrow Articles by Das, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Majka, S.
Right arrow Articles by Das, A.
(Investigative Ophthalmology and Visual Science. 2002;43:260-266.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Regulation of Matrix Metalloproteinase Expression by Tumor Necrosis Factor in a Murine Model of Retinal Neovascularization

Susan Majka1, Paul G. McGuire1,2 and Arup Das1,2,3

1 From the Division of Ophthalmology and the 2 Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico; and 3 Veterans Administration Medical Center, Albuquerque, New Mexico.

PURPOSE. Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through the regulation of extracellular proteinase production. It has been shown that matrix metalloproteinases (MMPs) are elevated in the retina during the neovascularization process. However, the factors and mechanisms that regulate the expression of these enzymes are not well characterized. The present study examines the potential role of tumor necrosis factor (TNF)-{alpha} as a regulator of MMPs in the retinal neovascularization process.

METHODS. C57/Bl6 mice were treated with 75% oxygen (experimental) or room air (control) from postnatal days (P)7 through P12, followed by room air until P17. Retinas were collected at P13, P15, or P17 and total RNA analyzed for the relative level of TNF{alpha}, TNF receptor (p55), and TNF{alpha}-converting enzyme (TACE). Immunostaining was used to identify changes in TNF protein expression as well as to localize TNF{alpha} within specific retinal cell types. The role of TNF{alpha} in stimulating retinal microvascular endothelial cell (RMVEC) proteinase production was evaluated using isolated murine RMVECs grown in normoxic or hypoxic conditions. Message expression was analyzed by RT-PCR and protein expression by zymographic analysis.

RESULTS. TNF{alpha} mRNA was increased in the retinas of experimental animals on P13 and P15, during the early stages of retinal neovascularization. In addition to being expressed by Müller glial cells and the inner nuclear layer, additional expression was noted in the outer nuclear layer of experimental animals. No significant level of apoptosis was detected in the retina of experimental animals with retinal neovascularization. Isolated RMVECs did not significantly increase MMP production directly in response to a hypoxic stimulus, but required the presence of exogenous TNF{alpha}. TNF{alpha} increased the expression of MT1-MMP, MMP-3, and MMP-9 in these cells. The levels of TACE and p55, proteins important in mediating the response of cells to TNF{alpha}, were found to be increased by the angiogenic protein, vascular endothelial growth factor (VEGF), which was also elevated in the experimental retinas.

CONCLUSIONS. TNF{alpha} levels increase in experimental mouse retinas exposed to hypoxic stimuli. Increased production of MMPs by RMVECs does not occur directly in response to a hypoxic stimulus. These cells are responsive, however, to stimulation by TNF{alpha}, which enhances the production of specific members of the MMP family. VEGF also plays a role in this process through its regulation of TACE and p55 mRNA in the vascular endothelial cells. These findings support the hypothesis that these two growth factors have a role in the regulation of extracellular proteinase expression during retinal neovascularization.




This article has been cited by other articles:


Home page
 IOVSHome page
F. Giansanti, M. Ramazzotti, L. Vannozzi, E. Rapizzi, T. Fiore, B. Iaccheri, D. Degl' Innocenti, D. Moncini, and U. Menchini
A Pilot Study on Ocular Safety of Intravitreal Infliximab in a Rabbit Model
Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1151 - 1156.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Charbonneau, K. Harper, F. Grondin, M. Pelmus, P. P. McDonald, and C. M. Dubois
Hypoxia-inducible Factor Mediates Hypoxic and Tumor Necrosis Factor {alpha}-induced Increases in Tumor Necrosis Factor-{alpha} Converting Enzyme/ADAM17 Expression by Synovial Cells
J. Biol. Chem., November 16, 2007; 282(46): 33714 - 33724.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
E. S. Colombo, G. Menicucci, P. G. McGuire, and A. Das
Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis through Increased Urokinase Expression
Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1793 - 1800.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
B. Zhao, G. Smith, J. Cai, A. Ma, and M. Boulton
Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2
Br. J. Ophthalmol., April 1, 2007; 91(4): 538 - 545.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. Kociok, S. Radetzky, T. U. Krohne, C. Gavranic, and A. M. Joussen
Pathological but Not Physiological Retinal Neovascularization Is Altered in TNF-Rp55-Receptor-Deficient Mice
Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5057 - 5065.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Z. Xu, Y. Yu, and E. J. Duh
Vascular Endothelial Growth Factor Upregulates Expression of ADAMTS1 in Endothelial Cells through Protein Kinase C Signaling.
Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4059 - 4066.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. Malik, K. Day, I. Perrault, D.S. Charnock-Jones, and S. K. Smith
Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-{alpha} in menstrual endometrium and effluent in women with menorrhagia
Hum. Reprod., August 1, 2006; 21(8): 2158 - 2166.
[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
 Arch OphthalmolHome page
S. W. Cousins, D. G. Espinosa-Heidmann, and K. G. Csaky
Monocyte Activation in Patients With Age-Related Macular Degeneration: A Biomarker of Risk for Choroidal Neovascularization?
Arch Ophthalmol, July 1, 2004; 122(7): 1013 - 1018.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. Castellon, S. Caballero, H. K. Hamdi, S. R. Atilano, A. M. Aoki, R. W. Tarnuzzer, M. C. Kenney, M. B. Grant, and A. V. Ljubimov
Effects of Tenascin-C on Normal and Diabetic Retinal Endothelial Cells in Culture
Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2758 - 2766.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Association for Research in Vision and Ophthalmology