Abstract
• Background: Formation of epiretinal membranes occurs in proliferative vitreoretinopathy, macular pucker and after penetrating trauma. Epiretinal membrane formation includes cell migration and proliferation, extracellular matrix formation and tissue contraction. Generally in scar tissue formation, the production of new extracellular matrix occurs concomitantly with its proteolytic degradation, resulting in continuous tissue remodelling. The plasminogen activator-mediated proteolytic cascade is an important mechanism for pericellular degradation of the extracellular matrix. Therefore we wanted to study the presence of the plasminogen activator-mediated proteolytic cascade in epiretinal membranes. • Methods: Specimens of 18 epiretinal and 3 subretinal membranes were obtained during vitreous surgery for retinal detachment with proliferative 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 epiretinal 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 membranes. Immunofluorescence staining localized urokinase predominantly in the areas invaded by macrophages and cells of retinal pigment epithelial origin. • Conclusion: Our results demonstrate the presence of proteolytic activity in periretinal scar tissue. Urokinase was more consistently present, but smaller amounts of tissue-type plasminogen activator were 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.
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References
Brinkedal-Hansen H (1993) Matrix metalloproteinases. J Periodontol 64:477–484
Clarkson JG, Green WR, Massof D (1977) A histopathologic review of 168 cases of preretinal membrane. Am J Ophthalmol 84:1–17
Gailit J, Clark RAF (1994) Wound repair in the context of extracellular matrix. Curr Opin Cell Biol 6:717–725
Granelli-Piperno A, Reich E (1978) A study of protease and protease-inhibitor complexes in biological fluids. J Exp Med 146:223–234
Greven CM, Slusher MM, Weaver RG (1988) Epiretinal membrane release and posterior vitreous detachment. Ophthalmology 95:902–905
Immonen I, Stephens RW, Salonen EM, Laatikainen L, Sim P-S, Vaheri A (1989) Tissue-type plasminogen activator in subretinal fluid. Curr Eye Res 8:249–252
Immonen I, Konttinen YT, Sorsa T, Tommila P, Siren V (1996) Proteinases in subretinal fluid. Graefe's Arch Clin Exp Ophthalmol 234:105–109
Kristensen P, Larsson LI, Nielsen LS, Grøndahl-Hansen J, Andreasen PA, Danø K (1984) Human endothelial cells contain one type of plasminogen activator. FEBS Lett 168:33–37
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Liotta LA, Goldfarb RH, Brundale R, Siegal GP, Terranova V, Garbiza S (1981) Effect of plasminogen activator (urokinase), plasmin and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res 41:4629–4636
Mietz H, Walshe R, Wiedemann P, Heimann K, Green WR (1994) Histopathologic study of epiretinal proliferations after vitrectomy with daunomycin and silicone oil. Retina 5:425–429
Morino I, Hiscott P, McKehnie N, Grierson I (1990) Variation in epiretinal membrane components with clinic duration of the proliferative tissue. Br J Ophthalmol 74:393–399
Niedbala MJ, Picarella MS (1992) Tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator mediated proteolysis of extracellular matrix and its antagonism by γ-interferon. Blood 79:678–687
Pöllänen J, Saksela O, Salonen E-M, Andreasen P, Nielsen L, Danø K, Vaheri A (1987) Distinct localization of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells. J Cell Biol 104:1085–1096
Pöllänen J, Stephens RW, Vaheri A (1991) Directed plasminogen activation at the surface of normal and malignant cells. Adv Cancer Res 57:273–328
Ronne E, Behrendt N, Ellis V, Ploug M, Danø K, Høyer-Hansen G (1991) Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2 terminal domain of the urokinase receptor. FEBS Lett 288:233–236
Sirén V, Stephens RW, Salonen E-M, Vaheri A, Summanen P, Immonen I (1992) Retinal pigment epithelial cells secrete urokinase-type plasminogen activator and its inhibitor PAI-1. Ophthalmic Res 24:203–212
Sirén V, Vaheri A, Immonen I (1994) Secretion of plasminogen activators by cells cultured from subretinal fluid. Acta Ophthalmol 72:218–222
Stephens RW, Pöllänen J, Tapiovaara H, Leung KC, Sim PS, Salonen E-M, Rønne G, Behrendt N, Danø K, Vaheri A (1989) Activation of pro-urokinase and plasminogen on human sarcoma cells. A proteolysic system with surface-bound reactants. J Cell Biol 108:1987–1995
Tervo K, Latvala T, Suomalainen V-P, Tervo T, Immonen I (1995) Cellular fibronectin and tenascin in experimental perforating scleral wounds with incarceration of the vitreous. Graefe's Arch Clin Exp Ophthalmol 233:168–172
Tripathi BJ, Geanon JD, Tripathi RC (1987) Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study. Ophthalmology 94:1434–1438
Unkeless JC, Gordon S, Reich E (1974) Secretion of plasminogen activator by stimulated macrophages. J Exp Med 139:834–850
Vaheri A, Bizik J, Salonen E-M, Tapiovaara H, Sirén V, Myöhänen H, Stephens RW (1989) Regulation of the pericellular activation of plasminogen and its role in tissue-destructive processes. Acta Ophthalmol (Copenh) [Suppl 202] 70:34–41
Wiedemann P, Heimann K (1992) Proliferative vitreoretinopathy. Curr Opin Ophthalmol 3:357–365
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Immonen, I., Vaheri, A., Tommila, P. et al. Plasminogen activation in epiretinal membranes. Graefe's Arch Clin Exp Ophthalmol 234, 664–669 (1996). https://doi.org/10.1007/BF00292351
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DOI: https://doi.org/10.1007/BF00292351