PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular barrier. A model for retinal edema.
VEGF is considered as an important factor in the pathogenesis of macular edema. VEGF induces the rupture of the blood retinal barrier and may also influence the retinal pigment epithelial (RPE) outer retinal barrier. The aim of this work was to analyze the influence of the VEGF receptor pathways in the modulation of the RPE barrier breakdown in vitro and in vivo. The ARPE19 human junctions in culture are modulated by VEGF through VEGFR-1 but not through VEGFR-2. PlGF-1, that is a pure agonist of VEGFR-1, is produced in ARPE-19 cells under hypoxic conditions and mimics VEGF effects on the external retinal barrier as measured by TER and inulin flux. In vivo, the intravitreous injection of PlGF-1 induces a rupture of the external retinal barrier together with a retinal edema. This effect is reversible within 4 days. VEGF-E, that is a pure agonist of VEGFR-2, does not induce any acute effect on the RPE barrier. These results demonstrate that PlGF-1 can reproduce alterations of the RPE barrier occurring during diabetic retinopathy.
Miyamoto
N
N
INSERM, UMRS 872, Equipe 17, Centre de Recherche des Cordeliers, Paris, France.
de Kozak
Y
Y
Normand
N
N
Courtois
Y
Y
Jeanny
J C
JC
Benezra
D
D
Behar-Cohen
F
F
D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006133:Growth Substances; D006801:Humans; D007150:Immunohistochemistry; D007444:Inulin / Q000493:pharmacokinetics; D008269:Macular Edema / Q000378:metabolism* / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis* / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
D006133:Growth Substances; C000608036:PGF protein, human; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D007444:Inulin; D004247:DNA; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2