[en] 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 Pig, 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.
Disciplines :
Ophthalmology
Author, co-author :
Rakic, Jean-Marie ; Université de Liège - ULiège > Département des sciences cliniques > Ophtalmologie
Lambert, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Ophtalmologie
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Bajou, Khalid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Peyrollier, Karine
Alvarez Gonzalez, Maria-Luz ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Carmeliet, Peter
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Language :
English
Title :
Mice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization
Publication date :
April 2003
Journal title :
Investigative Ophthalmology and Visual Science
ISSN :
0146-0404
eISSN :
1552-5783
Publisher :
Assoc Research Vision Ophthalmology Inc, Bethesda, United States - Maryland
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