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TitrePlacental growth factor (PlGF) inhibition reduces choroidal neovascularization in a mouse model for age-related macular degeneration (ARMD)
Abstract Nr.144
ButTo evaluate whether and through which mechanism PlGF blockage can inhibit choroidal neovascularization (CNV) in a mouse model of age-related macular degeneration.
MéthodesCNV was induced in mice by placing 3 Argon laser burns on the choroid. In a first experiment we compared CNV formation between PlGF knock-out and wild type mice. Secondly, 144 wild-type mice were injected every 2 days with 5, 10, 20 or 40 mg/kg of either an anti-PlGF-antibody, an anti-VEGF receptor-2 (VEGFR2) antibody or an irrelevant control antibody. The CNV lesions were evaluated on histological cross-sections. The amount of endothelial cells, pericytes and inflammatory cells in the lesions were morphometrically analyzed after immunostaining for CD31, smooth muscle alpha-actin and F4/80 respectively.
RésultatsCNV formation was significantly reduced in the PlGF knockout mice. The dose-response experiment showed that the 20 mg/kg dose of anti-PlGF significantly reduced the number of vessels in the lesions as compared to control antibody (p= 0.045), although less than a comparable dose of anti-VEGFR2-antibody (p= 0.027). Moreover, smooth muscle cell coverage was significantly increased in the anti-PlGF treated (p= 0.02) and reduced in the anti-VEGFR2 treated mice (p= 0.51) as compared to control mice. Finally, a significant reduction in number of inflammatory cells was observed in the lesions treated with anti-PlGF treated (p= 0.01) but not in the anti-VEGFR-2 treated mice (p= 0.30).
ConclusionAnti-PlGF treatment inhibits CNV formation in a mouse model for ARMD. Both anti-PlGF and anti-VEGFR2 impair capillary growth, but in contrary to VEGFR2 blockage, anti-PlGF also reduces inflammation and promotes vessel maturation.
Auteur 1
NomVAN DE VEIRE
InitialesS
InstitutKULeuven
VilleLeuven
Auteur 2
NomMoons
InitialesL
InstitutKULeuven
VilleLeuven
Auteur 3
NomVinores
InitialesS
InstitutKULeuven
VilleLeuven
Auteur 4
NomCarmeliet
InitialesP
InstitutKULeuven
VilleLeuven
Auteur 5
NomStalmans
InitialesI
InstitutKULeuven
VilleLeuven
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