VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy

TY - JOUR

T1 - VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy

AU - Cao, Renhai

AU - Xue, Yuan

AU - Hedlund, Eva-Maria

AU - Zhong, Zhaodong

AU - Tritsaris, Katerina

AU - Tondelli, Barbara

AU - Lucchini, Franco

AU - Zhu, Zhenping

AU - Dissing, Steen

AU - Cao, Yihai

PY - 2010/1

Y1 - 2010/1

N2 - 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 ligandmediated retinopathy, and define VEGFR1 as an important target of antiangiogenic therapy for treatment of retinopathy.

AB - 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 ligandmediated retinopathy, and define VEGFR1 as an important target of antiangiogenic therapy for treatment of retinopathy.

U2 - 10.1073/pnas.0911661107

DO - 10.1073/pnas.0911661107

M3 - Journal article

C2 - 20080765

SN - 0027-8424

VL - 107

SP - 856

EP - 861

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 2

ER -