TY - JOUR
T1 - Mice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization.
AU - Rakic, Jean-Marie
AU - Lambert, Vincent
AU - Munaut, Carine
AU - Bajou, Khalid
AU - Peyrollier, Karine
AU - Alvarez-Gonzalez, Marie-Luz
AU - Carmeliet, Peter
AU - Foidart, Jean-Michel
AU - Noël, Agnès
N1 - Keywords: Aged; Aged, 80 and over; Animals; Choroidal Neovascularization; Disease Models, Animal; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; Humans; Laser Coagulation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Plasminogen; RNA, Messenger; Receptors, Cell Surface; Reverse Transcriptase Polymerase Chain Reaction; Tissue Plasminogen Activator; Urinary Plasminogen Activator
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 12657615
VL - 44
SP - 1732
EP - 1739
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
SN - 0146-0404
IS - 4
ER -