April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Terpestacin Inhibits Retinal Neovascularization via Blockade of Mitochondrial Complex III
Author Affiliations & Notes
  • Myoung Seok Jeong
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea
  • Yo Han Bae
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea
  • Ja Young Jung
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea
  • Ho Jeong Kwon
    Translational Research Center for Protein Function Control, Department of Biotechnology, Yonsei University, Seoul, Republic of Korea
  • Young Suk Yu
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea
  • Jeong Hun Kim
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  Myoung Seok Jeong, None; Yo Han Bae, None; Ja Young Jung, None; Ho Jeong Kwon, None; Young Suk Yu, None; Jeong Hun Kim, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4882. doi:
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      Myoung Seok Jeong, Yo Han Bae, Ja Young Jung, Ho Jeong Kwon, Young Suk Yu, Jeong Hun Kim; Terpestacin Inhibits Retinal Neovascularization via Blockade of Mitochondrial Complex III. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4882.

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Abstract

Purpose: : To investigate whether inhibitory effect of terpestacin on retinal neovascularization of oxygen-induced retinopathy (OIR).

Methods: : After intravitreal injection of terpestacin in OIR mice, retinal neovascularization was examined by fluorescence angiography and vessel counting in cross sections. Then, anti-angiogenic activity of terpestacin was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration and in vitro tube formation assay of human retinal microvascular endothelial cells (HRMECs). To determine whether terpestacin affected the function of UCQRB, we measured the reactive oxygen species (ROS) level and the expression of hypoxia inducible factor-1alpha (HIF-1a) by treating terpestacin on hypoxic HRMECs, using 2', 7'-dichlorofluorescein diacetate(DCF-DA) and western blot analysis, respectively.

Results: : Terpestacin inhibited angiogenesis in vivo, which suppressed in OIR, as identified through fluorescence angiography and vessel counting. In addition, terpestacin significantly decreased VEGF-induced proliferation, migration and tube formation of HRMECs in optimal condition. Terpestacin also reduced the ROS generation by blocking UQCRB, which initiated the destabilization of HIF-1a on hypoxic HRMECs.

Conclusions: : Our data suggests that terpestacin has anti-angiogenic effects through the blockade of UQCRB, which significantly inhibits retinal neovascularization.

Keywords: retinal neovascularization • neovascularization • drug toxicity/drug effects 
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