June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The role of VEGFR-3 in the pathogenesis of choroidal neovascularization in age-related macular degeneration
Takeshi Yoshida; Shikun He; Mizuki Kitamura; Christine Spee; Stephen Ryan; David Hinton
Author Affiliations & Notes
  • Takeshi Yoshida
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Department of Ophthalmology, Tokyo Medical and Dental University, Bunkyo, Japan
  • Shikun He
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Departments of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • Mizuki Kitamura
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • Christine Spee
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • Stephen Ryan
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Departments of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • David Hinton
    Ophthalmology, Doheny Eye Institution, Los Angeles, CA
    Departments of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • Footnotes
    Commercial Relationships Takeshi Yoshida, None; Shikun He, None; Mizuki Kitamura, None; Christine Spee, None; Stephen Ryan, Alergan (S); David Hinton, RPT (I), RPT (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 334. doi:
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      Takeshi Yoshida, Shikun He, Mizuki Kitamura, Christine Spee, Stephen Ryan, David Hinton; The role of VEGFR-3 in the pathogenesis of choroidal neovascularization in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):334.

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Abstract

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Recently, it’s reported that VEGFR-3 has a potential role in the pathogenesis of angiogenesis. The aim of the present study is to investigate the role of VEGFR-3 induced by interferon gamma IFNγ in the development of CNV in vitro.

Methods: Cryostat retinal sections from laser-induced CNV eyes of C57/BL6 mice were used for immunohistochemistry of VEGFR-3. IFNγ-induced VEGF-C in cultured human fetal retinal pigment epithelium cells (RPE) was analyzed by western blotting, and IFNγ-induced VEGFR-3 in human umbilical vein endothelial cells (HUVEC) was analyzed as well. HUVEC were transfected with scrambled or VEGFR-3 siRNA and then treated with or without IFNγ. The cells were stimulated with supernatant of RPE with or without IFNγ, and the angiogenic activity was measured using tube-formation assay. Furthermore, induction of VEGFR-2/VEGFR-3 heterodimer in HUVEC by the RPE supernatant was examined by immunoprecipitation and western blotting.

Results: Markedly increased expression of VEGFR-3 was observed in RPE and endothelial cells in mouse CNV lesions induced by laser. In vitro, RPE stimulated with IFNγ significantly increased VEGF-C expression in supernatant of the RPE. In scrambled siRNA transfected RPE, pretreatment of HUVEC with IFNγ and treatment with the supernatant of IFNγ-treated RPE induced marked angiogenesis in tube formation assay; however, the angiogenic effect was diminished by inhibition of VEGFR-3 using siRNA in HUVECs. Furthermore, the supernatant treatment mentioned above also upregulated expression of VEGFR-2/VEGFR-3 heterodimer and phospho-ERK1/2 in HUVEC. VEGFR3 knockdown by siRNA also diminished the expression of the heterodimer and phospho-ERK1/2 in HUVEC.

Conclusions: Our data shows that VEGFR-3 and VEGF-C induced by IFNγ play an important role in angiogenesis. These results suggest that they might be a new therapeutic target for the treatment of wet AMD.

Keywords: 412 age-related macular degeneration • 453 choroid: neovascularization • 701 retinal pigment epithelium  
© 2013, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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