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

Franco Lucchini, Renhai Cao, Yuan Xue, Eva-Maria Hedlund, Zhaodong Zhong, Katerina Tritsaris, Barbara Tondelli, Zhenping Zhu, Steen Dissing, Yihai Cao

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)856-861
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Publication statusPublished - 2010

Keywords

  • angiogenesis
  • antiangiogenic therapy
  • mural cells
  • neovascularization
  • vascular permeability

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