title: Mice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization.
abstract: 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.
authors.affiliation: Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium. jmrakic@chu.ulg.ac.be
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Khalid
authors.initials: K
authors.lastname: Bajou
authors.forename: Karine
authors.initials: K
authors.lastname: Peyrollier
authors.forename: Marie-Luz
authors.initials: ML
authors.lastname: Alvarez-Gonzalez
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
mesh_terms: 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*
chemical_list: 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