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 Science of the United States of America
JF - Proceedings of the National Academy of Science of the United States of America
IS - 2
ER -
