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1From the Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium; the 2Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium; and the 3Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Belgium.
PURPOSE. To evaluate the presence and potential involvement of members of the plasminogen/plasminogen activator (Plg/PA) system in the exudative form of age-related macular degeneration (AMD).
METHODS. The expression of PA members mRNA was evaluated in human and experimental choroidal neovascularization (CNV) by RT-PCR. The presence and activity of PA was studied by immunofluorescence and in situ zymography. The influence of endogenous plasminogen (Plg), urokinase (uPA), tissue type plasminogen activator (tPA), and uPA receptor (uPAR) was explored in single-gene-deficient mice in a model of laser-induced CNV.
RESULTS. Members of the Plg/PA system were present both in human and murine CNV. The absence of Plg, uPA, or tPA significantly decreased the development of experimental CNV compared with wild-type or uPAR-deficient mice. This effect could be attributable, partly to a modulation of matrix metalloproteinase activity, but also to an accumulation of fibrinogen-fibrin in the laser-induced wounds.
CONCLUSIONS. Together with previous work done by the authors, this study indicates that choroidal neovascularization is extremely sensitive to the modulation of Plg/PA system activity. This may provide a new strategy for the treatment of exudative AMD.
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