Laser trabeculoplasty induces stromelysin expression by trabecular juxtacanalicular cells

Dorothy E. Parshley, John M.B. Bradley, Aurelie Fisk, Anoushirvan Hadaegh, John R. Samples, E. Van Michael Buskirk, Ted S. Acott

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Purpose. The mechanism by which laser trabeculoplasty reduces elevated intraocular pressure in primary open-angle glaucoma has not been established. To test the hypothesis that trabecular extracellular matrix turnover is involved, stromelysin expression after laser treatment of anterior segment organ cultures was evaluated. Methods. Argon laser trabeculoplasty, using typical clinical treatment parameters, was applied to anterior segment organ cultures. Stromelysin levels and activity were then evaluated at various times by immunoblots of Western transfers and by zymography. Stromelysin mRNA levels were evaluated by dot blot and by reverse transcription, followed by polymerase chain reaction amplification. Stromelysin protein was localized by immunohistochemistry, and image analysis was used for quantitation. Stromelysin mRNA was localized by in situ hybridization. Results. Trabecular stromelysin protein, activity, and mRNA levels were detectably elevated by 8 hours and were several-fold higher by 24 hours after treatment. Stromelysin immunostaining was elevated dramatically in the justacanalicular and inserts regions of the meshwork, but only modestly in other regions. Stromelysin mRNA increases also were localized primarily to these regions. The juxtacanalicular strumelysin immunostaining increase was sustained for at least 1 week, whereas the insert levels declined somewhat after day 2. Conclusions. A stromelysin increase, localized primarily to the juxtacanalicular region of the meshwork, the putative site of the aqueous tumor outflow resistance, should degrade trabecular proteoglycans, the putative outflow resistance source, and allow their uptake and further degradation by the juxtacanalicular cells. If diminished juxtacanalicular extracellular matrix turnover is responsible for the glaucomatous reduction in aqueous humor outflow, an increase in stromelysin in this specific area of the meshwork should ameliorate the problem. Thus, the observations support the working hypothesis and may explain the efficacy of this treatment for glaucoma.

Original languageEnglish (US)
Pages (from-to)795-804
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number5
StatePublished - 1996

Keywords

  • glaucoma
  • laser trabeculoplasty
  • matrix metalloproteinase
  • stromelysin
  • trabecular extracellular matrix

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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