PLASMINOGEN ACTIVATION IN EPIRETINAL MEMBRANES

Background: Formation of epiretinal membranes occurs in proliferative vitreoretinopathy, macular pucker and after penetrating trauma. Epiret inal membrane formation includes cell migration and proliferation, ext racellular matrix formation and tissue contraction. Generally in scar tissue formation, the production of new extracellular matrix occurs co ncomitantly with its proteolytic degradation, resulting in continuous tissue remodelling. The plasminogen activator-mediated proteolytic cas cade is an important mechanism for pericellular degradation of the ext racellular matrix. Therefore we wanted to study the presence of the pl asminogen activator-mediated proteolytic cascade in epiretinal membran es. Methods: Specimens of Is epiretinal and 3 subretinal membranes wer e obtained during vitreous surgery for retinal detachment with prolife rative vitreoretinopathy or macular pucker. Plasminogen activators and plasmin were characterized in frozen sections of epiretinal membranes by in situ zymography and in membrane lysates by zymography. Indirect immunofluorescence staining was performed to localize urokinase in ep iretinal membranes. Results: Urokinase was present in 17/21 and tissue -type plasminogen activator in 12/21 of the membranes studied. Active plasmin was not detected in the frozen sections of epiretinal membrane s. Immunofluorescence staining localized urokinase predominantly in th e areas invaded by macrophages and cells of retinal pigment epithelial origin. Conclusion: Our results demonstrate the presence of proteolyt ic activity in periretinal scar tissue. Urokinase was more consistentl y present, but smaller amounts of tissue-type plasminogen activator we re also found in the specimens. These results indicate that continuous tissue remodelling with simultaneous extracellular matrix production and breakdown regulates the growth of epiretinal membranes.