Differential expression of matrix metalloproteinases 2 and 9 by glial Müller cells: response to soluble and extracellular matrix-bound tumor necrosis factor-alpha

Am J Pathol. 2002 May;160(5):1847-55. doi: 10.1016/s0002-9440(10)61131-5.


Glial Müller cells are known to undergo functional and morphological changes during retinal proliferative disorders, but very little is known of the contribution of these cells to extracellular matrix deposition during retinal wound healing and gliosis. This study constitutes the first demonstration that retinal Müller cells express two major matrix metalloproteinases (MMPs), gelatinase A (MMP-2) and gelatinase B (MMP-9), implicated in cell migration and matrix degradation. Although mRNA and gelatinolytic activity of MMP-2 remained unchanged in cultured Müller cells, basal levels of MMP-9 mRNA observed after subculture at 24 hours, markedly declined after 48 or 72 hours. This correlated with the expression of MMP-9 gelatinolytic activity that peaked at 24 hours, but gradually decreased at 48 and 72 hours. Tumor necrosis factor-alpha, in both a soluble form or bound to collagen and fibronectin, increased MMP-9 mRNA and gelatinolytic activity, but not MMP-2 expression, and its effect could be blocked by anti-tumor necrosis factor-alpha antibodies. The results suggest that Müller cells may aid in the local control of extracellular matrix deposition during retinal proliferative disorders, and that interaction of these cells with matrix-bound cytokine may influence their pathological behavior. Control of Müller cell production of MMP-9 may constitute an important target for the design of new therapeutic approaches to treat and prevent retinal proliferative disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Cells, Cultured
  • Collagen / metabolism
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / metabolism
  • Female
  • Fibronectins / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Middle Aged
  • Protein Binding
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retina / cytology
  • Retina / drug effects
  • Retina / enzymology*
  • Solubility
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antibodies, Monoclonal
  • Fibronectins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9