Mediation of laser trabeculoplasty-induced matrix metalloproteinase expression by IL-1β and TNFα

John M.B. Bradley, Ann Marie Anderssohn, Christine M. Colvis, Dorothy E. Parshley, Xiang Hong Zhu, Michael S. Ruddat, John R. Samples, Ted S. Acott

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Purpose. Laser trabeculoplasty of the anterior uveal region of the trabecular meshwork induces sustained matrix metalloproteinase expression within the juxtacanalicular region of the meshwork. Studies were conducted to test the hypothesis that a factor mediates this response and to identify the factor. Methods. Human anterior segment organ cultures were subjected to laser treatment using standard clinical parameters and were returned to culture for 8 hours. The resultant 8-hour-conditioned culture medium was then tested for factor activity by evaluating its ability to produce two typical trabecular responses to laser treatment, that is, to induce stromelysin expression or to trigger cell division, when applied to fresh organ cultures or to cell cultures. Confocal immunohistochemistry of the laser-treated organ cultures and western immunoblot analysis of the conditioned medium were used to evaluate changes in potential candidates for the factor activity. The ability of the interleukin (IL)-1 receptor antagonist (IL-1ra)- and of tumor necrosis factor alpha (TNFα)-blocking antibodies to eliminate the stromelysin induction was evaluated. Results. Medium conditioned for 8 hours induced typical trabecular cell division in anterior segment organ cultures. Medium conditioned for 8 hours, but not for 30 minutes, induced typical increases in stromelysin expression in these organ cultures and in cell cultures. After 8 hours, both trabecular cells in laser-treated organ cultures and in the conditioned medium contained elevated levels of IL-1β and TNFα. The laser-treated organ cultures contained elevated levels of IL- 1α, but it was not secreted into the medium. The ability of conditioned media to induce stromelysin expression was partially blocked by either the IL-1ra- or the TNFα-blocking antibody. Conclusions. Laser trabeculoplasty induces the expression and secretion of both IL-1β and TNFα within the first 8 hours after treatment. These cytokines then mediate increased trabecular stromelysin expression. Putatively, this initiates remodeling of the juxtacanalicular extracellular matrix, a likely site for the aqueous outflow resistance, and thus restores normal outflow facility.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume41
Issue number2
StatePublished - Feb 15 2000

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Bradley, J. M. B., Anderssohn, A. M., Colvis, C. M., Parshley, D. E., Zhu, X. H., Ruddat, M. S., Samples, J. R., & Acott, T. S. (2000). Mediation of laser trabeculoplasty-induced matrix metalloproteinase expression by IL-1β and TNFα. Investigative Ophthalmology and Visual Science, 41(2), 422-430.