Mice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization.
OBJECTIVE
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.
Rakic
Jean-Marie
JM
Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium. jmrakic@chu.ulg.ac.be
Lambert
Vincent
V
Munaut
Carine
C
Bajou
Khalid
K
Peyrollier
Karine
K
Alvarez-Gonzalez
Marie-Luz
ML
Carmeliet
Peter
P
Foidart
Jean-Michel
JM
Noël
Agnès
A
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000235:genetics*
C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator