VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy.
Proc Natl Acad Sci U S A
; 107(2): 856-61, 2010 Jan 12.
Article
en En
| MEDLINE
| ID: mdl-20080765
ABSTRACT
VEGF coordinates complex regulation of cellular regeneration and interactions between endothelial and perivascular cells; dysfunction of the VEGF signaling system leads to retinopathy. Here, we show that systemic delivery of VEGF and placental growth factor (PlGF) by protein implantation, tumors, and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photoreceptors and ganglion cells. Moreover, blockade of VEGFR1 but not VEGFR2 significantly restores pericyte saturation in mature retinal vessels. Our findings link VEGF and PlGF to cancer-associated retinopathy, reveal the molecular mechanisms of VEGFR1 ligand-mediated retinopathy, and define VEGFR1 as an important target of antiangiogenic therapy for treatment of retinopathy.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Enfermedades de la Retina
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Pericitos
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Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Factor A de Crecimiento Endotelial Vascular
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Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2010
Tipo del documento:
Article
País de afiliación:
Suecia