Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human... Glaucomatous optic neuropathy is a common blinding disease characterized by remodeling of the extracellular matrix (ECM) and loss of retinal ganglion cell (RGC) axons at the level of the optic nerve head (ONH). Astrocytes, the major cell type in ONH, may participate in this process by production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). In normal and glaucomatous ONH, we detected MMP and TIMP expression by immunohistochemistry. Cultured astrocytes were used to characterize expression of MMPs and TIMPs by zymography, Western blot, and RNase protection assay. MMP production was stimulated with phorbol 12‐myristate 13‐acetate (PMA). Astrocytes expressed MMP1, MT1‐MMP, MMP2, TIMP1, and TIMP2 in normal and glaucomatous ONH. MMP2, TIMP1, and TIMP2 localized to RGCs and their axons. Increased MMP1 and MT1‐MMP expression was demonstrated in glaucoma. Cultured astrocytes constitutively expressed MMP2, MT1‐MMP, TIMP1, and TIMP2, whereas MMP3, MMP7, MMP9, and MMP12 were not detectable in tissues or in cultured astrocytes. Our findings demonstrate the presence of specific MMPs and TIMPs in the ONH that may participate in the homeostasis and remodeling of the ECM in glaucoma. Expression of the same MMPs and TIMPs in cultured ONH astrocytes will allow further studies on the mechanisms regulating these enzymes. GLIA 33:205–216, 2001. © 2001 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Glia Wiley

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes

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Publisher
Wiley
Copyright
Copyright © 2001 Wiley‐Liss, Inc.
ISSN
0894-1491
eISSN
1098-1136
D.O.I.
10.1002/1098-1136(200103)33:3<205::AID-GLIA1019>3.0.CO;2-D
Publisher site
See Article on Publisher Site

Abstract

Glaucomatous optic neuropathy is a common blinding disease characterized by remodeling of the extracellular matrix (ECM) and loss of retinal ganglion cell (RGC) axons at the level of the optic nerve head (ONH). Astrocytes, the major cell type in ONH, may participate in this process by production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). In normal and glaucomatous ONH, we detected MMP and TIMP expression by immunohistochemistry. Cultured astrocytes were used to characterize expression of MMPs and TIMPs by zymography, Western blot, and RNase protection assay. MMP production was stimulated with phorbol 12‐myristate 13‐acetate (PMA). Astrocytes expressed MMP1, MT1‐MMP, MMP2, TIMP1, and TIMP2 in normal and glaucomatous ONH. MMP2, TIMP1, and TIMP2 localized to RGCs and their axons. Increased MMP1 and MT1‐MMP expression was demonstrated in glaucoma. Cultured astrocytes constitutively expressed MMP2, MT1‐MMP, TIMP1, and TIMP2, whereas MMP3, MMP7, MMP9, and MMP12 were not detectable in tissues or in cultured astrocytes. Our findings demonstrate the presence of specific MMPs and TIMPs in the ONH that may participate in the homeostasis and remodeling of the ECM in glaucoma. Expression of the same MMPs and TIMPs in cultured ONH astrocytes will allow further studies on the mechanisms regulating these enzymes. GLIA 33:205–216, 2001. © 2001 Wiley‐Liss, Inc.

Journal

GliaWiley

Published: Mar 1, 2001

References

  • Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
    Anthony, Anthony; Ferguson, Ferguson; Matyzak, Matyzak; Miller, Miller; Esiri, Esiri; Perry, Perry
  • Membrane‐type 1 matrix metalloprotease (MT1‐MMP) enables invasive migration of glioma cells in central nervous system white matter
    Belien, Belien; Paganetti, Paganetti; Schwab, Schwab
  • Computational sequence analysis of the tissue inhibitor of metalloproteinase family
    Douglas, Douglas; Shi, Shi; Sang, Sang
  • The optic nerve head in glaucoma: role of astrocytes in tissue remodeling
    Hernandez, Hernandez
  • Differential regulation of tissue inhibitor of metalloproteinase mRNA expression in response to intracranial injury
    Jaworski, Jaworski
  • Expression of neural cell adhesion molecule (NCAM) characterizes a subpopulation of type 1 astrocytes in human optic nerve head
    Kobayashi, Kobayashi; Vidal, Vidal; Pena, Pena; Hernandez, Hernandez
  • Cytotoxicity by matrix metalloprotease‐1 in organotypic spinal cord and dissociated neuronal cultures
    Vos, Vos; Sjulson, Sjulson; Nath, Nath; McArthur, McArthur; Pardo, Pardo; Rothstein, Rothstein; Conant, Conant
  • Quantitation of matrix metalloproteinases in cultured rat astrocytes using the polymerase chain reaction with a multi‐competitor cDNA standard
    Wells, Wells; Catlin, Catlin; Cossins, Cossins; Mangan, Mangan; Ward, Ward; Miller, Miller; Clements, Clements

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