LASER TRABECULOPLASTY INDUCES STROMELYSIN EXPRESSION BY TRABECULAR JUXTACANALICULAR CELLS

Purpose. The mechanism by which laser trabeculoplasty reduces elevated intraocular pressure in primary open-angle glaucoma has not been esta blished. To test the hypothesis that trabecular extracellular matrix t urnover is involved, stromelysin expression after laser treatment of a nterior segment organ cultures was evaluated. Methods. Argon laser tra beculoplasty, using typical clinical treatment parameters, was applied to anterior segment organ cultures. Stromelysin levels and activity w ere then evaluated at various times by immunoblots of Western transfer s and by zymography. Stromelysin mRNA levels were evaluated by dot blo t and by reverse transcription, followed by polymerase chain reaction amplification. Stromelysin protein was localized by immunohistochemist ry, and image analysis was used for quantitation. Stromelysin mRNA was localized by in situ hybridization. Results, Trabecular stromelysin p rotein, 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 juxtacanalicular and i nsert regions of the meshwork, but only modestly in other regions. Str omelysin mRNA increases also were localized primarily to these regions . The juxtacanalicular stromelysin immunostaining increase was sustain ed for at least 1 week, whereas the insert levels declined somewhat af ter day 2. Conclusions. A stromelysin increase, localized primarily to the juxtacanalicular region of the meshwork, the putative site of the aqueous humor outflow resistance, should degrade trabecular proteogly cans, the putative outflow resistance source, and allow their uptake a nd further degradation by the juxtacanalicular cells. If diminished ju xtacanalicular extracellular matrix turnover is responsible for the gl aucomatous reduction in aqueous humor outflow, an increase in stromely sin in this specific area of the meshwork should ameliorate the proble m. Thus, the observations support the working hypothesis and may expla in the efficacy of this treatment for glaucoma.