June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
H-1129 suppresses neovascularization through inhibition of secretion of VEGF and proliferation of vascular endothelial cells
Author Affiliations & Notes
  • Yoko Yoshida
    D.Western Therapeutics Institute, Inc., Nagoya, Japan
    Human Research Promotion and Drug Development, Mie University, Tsu, Mie, Japan
  • Atsuko Kasai
    D.Western Therapeutics Institute, Inc., Nagoya, Japan
    Human Research Promotion and Drug Development, Mie University, Tsu, Mie, Japan
  • Hiroyoshi Hidaka
    D.Western Therapeutics Institute, Inc., Nagoya, Japan
    Human Research Promotion and Drug Development, Mie University, Tsu, Mie, Japan
  • Footnotes
    Commercial Relationships   Yoko Yoshida, D. Western Therapeutics Institute, Inc. (E); Atsuko Kasai, D. Western Therapeutics Institute, Inc. (E); Hiroyoshi Hidaka, D. Western Therapeutics Institute, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 191. doi:
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    • Get Citation

      Yoko Yoshida, Atsuko Kasai, Hiroyoshi Hidaka; H-1129 suppresses neovascularization through inhibition of secretion of VEGF and proliferation of vascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):191.

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

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Abstract

Purpose : We reported that H-1129 bound to Hsp90 specifically in ARVO2012. In this study, we elucidate the mechanism of action of H-1129 against neovascularization. It was investigated that effects of H-1129 on production of vascular endothelial growth factor (VEGF), migration of retinal pigment epithelial cells (RPE cells) and proliferation of vascular endothelial cells (VECs). Effects of H-1129 on hypoxia-inducible factor-1 (HIF-1) were also investigated. HIF-1, a transcription factor regulating expression of VEGF, is stabilized through Hsp90 action (Wu WC et al., 2007).

Methods : H-1129 was discovered, synthesized and patented by D. Western Therapeutics Institute, Inc. (DWTI) laboratory. VEGF concentration in the culture supernatant of ARPE-19 cells following pretreatment with H-1129 was measured by ELISA. Cell migration was assessed by wound healing assay and cell proliferation was assessed by Cell Counting Kit-8 assay. HIF-1 alpha, a subunit of HIF-1, in the cells was analyzed by Western blotting.

Results : H-1129 significantly reduced VEGF secretion from ARPE-19 cells and inhibited migration of ARPE-19 cells. H-1129 also inhibited proliferation of human retinal microvascular endothelial cells (hRMECs) and human umbilical vascular endothelial cells (HUVEC) in the presence of VEGF. Both H-1129 and its main metabolite, H-1129M1, reduced HIF-1 alpha in ARPE-19 cells cultured under hypoxic condition.

Conclusions : H-1129 inhibited cell proliferation of VECs, cell migration of RPE cells and secretion of VEGF from RPE cells. H-1129 and H-1129M1 reduced induction of HIF-1 alpha in RPE cells under hypoxic condition. These results suggest double-action mechanism of H-1129 for suppression of production of VEGF in RPE cells and inhibition of cell proliferation of VECs in the presence of VEGF stimulation. H-1129 has the possibility to become a superior therapeutic drug for choroidal neovascularization .

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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