July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
VEGFR2 and VEGF-C Suppress the Epithelial–Mesenchymal Transition via YAP in RPE Cells
Author Affiliations & Notes
  • Yuxiang Du
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Xiangke Yin
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Qishan Chen
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Lijuan Huang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Shasha Wang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Linbin Zhou
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Zhimin Ye
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Xiangrong Ren
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Hong Ouyang
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Xuri Li
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Rong Ju
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou, GuangDong, China
  • Footnotes
    Commercial Relationships   Yuxiang Du, None; Xiangke Yin, None; Qishan Chen, None; Lijuan Huang, None; Shasha Wang, None; Linbin Zhou, None; Zhimin Ye, None; Xiangrong Ren, None; Hong Ouyang, None; Xuri Li, None; Rong Ju, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4001. doi:https://doi.org/
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      Yuxiang Du, Xiangke Yin, Qishan Chen, Lijuan Huang, Shasha Wang, Linbin Zhou, Zhimin Ye, Xiangrong Ren, Hong Ouyang, Xuri Li, Rong Ju; VEGFR2 and VEGF-C Suppress the Epithelial–Mesenchymal Transition via YAP in RPE Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4001. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : RPE cells play critical roles in maintaining retinal homeostasis. Dysfunctions in RPE cells lead to ocular diseases including age-related macular degeneration (AMD), proliferative vitreoretinopathy (PVR) and Leber congenital amaurosis (LCA). It has been reported that RPE cells not only secrete VEGF-A to support choroidal vasculature, but also express VEGFR2, the receptor of VEGFs. Anti-VEGF-A drugs have been routinely used to inhibit ocular revascularization, and drugs targeting VEGFR2, are also under development, however, the impact of VEGF signaling inhibition on RPE cell functions, particularly epithelial–mesenchymal transition (EMT) of RPE, remains to be fully elucidated. The purpose of this study is to investigate the effects of VEGF signaling inhibition on EMT of RPE cells.

Methods : siRNAs were utilized to knock down expression of genes in both human primary RPE and ARPE-19 cells. Real-time quantitative PCR (RT-PCR) and Western blotting analysis were hired to investigate the expression of typical EMT markers, fibronectin, collagen I and the hippo pathway markers YAP, CTGF and CYR61. A neutralization antibody was used to block VEGF-A.

Results : We found VEGFR2 is required to inhibit epithelial–mesenchymal transition (EMT) in RPE cells. We further revealed that loss of VEGF-C rather than VEGF-A induces EMT in these cells. Mechanistically, we showed that the VEGFR2 ablation-induced EMT in RPEs is mediated by activation of YAP, an effector of the Hippo pathway.

Conclusions : Our results disclose unexpected novel roles of VEGFR2 and VEGF-C in the Hippo pathway and in the process of EMT of RPE cells. These results call attention to the potential risks in the fields of anti-VEGFR2 and anti-VEGF-C drug development.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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