May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Anti-Angiogenic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide in Retinal and Choroidal Angiogenesis
Author Affiliations & Notes
  • J. Kim
    Ophthalmology-Coll of Med, Seoul National Univ Hospital, Seoul, Republic of Korea
  • J. Kim
    Ophthalmology-Coll of Med, Seoul National Univ Hospital, Seoul, Republic of Korea
  • Y. Yu
    Ophthalmology-Coll of Med, Seoul National Univ Hospital, Seoul, Republic of Korea
  • H.-J. Kwon
    Bioengineering, Yonsei University, Seoul, Republic of Korea
  • K.-W. Kim
    Pharmacy, Seoul National Univ, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  J. Kim, None; J. Kim, None; Y. Yu, None; H. Kwon, None; K. Kim, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1382. doi:https://doi.org/
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      J. Kim, J. Kim, Y. Yu, H.-J. Kwon, K.-W. Kim; Anti-Angiogenic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide in Retinal and Choroidal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1382. doi: https://doi.org/.

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

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Abstract

Purpose: : Histone deacetylase (HDAC), a key enzyme in gene expression, regulates angiogenic cytokine expression via HIF-1α pathway. Here, we report a new synthetic small molecule, N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), as a HDAC inhibitor with anti-angiogenic activity to retinal and choroidal neovascularization both in vitro and in vivo.

Methods: : The toxicity of HNHA was evaluated through MTT assay in human umbilical vein endothelial cells (HUVECs) as well as histological examination and TUNEL staining in the HNHA-injected retina. In addition, the effect of HNHA on physiologic retinal angiogenesis in development was assessed. Anti-angiogenic activity of HNHA was evaluated by in vitro tube formation assay and cell invasion assay of HUVECs. In C57BL/6 mice with OIR and laser-induced CNV, HNHA was injected intravitreously. Retinal and choroidal angiogenesis were examined by fluorescence angiography and vessel counting in cross sections.

Results: : The compound inhibited HDAC enzyme activity as well as proliferation of HUVECs in vitro. Treatment of cells with HNHA elicited histone hyperacetylation leading to an up-regulation of p21 transcription, cell cycle arrest, and an inhibition of tube formation and cell invasion of HUVECs. Moreover, HNHA significantly reduces VEGF expression via down-regulation of HIF-1α. HNHA effectively inhibited retinal and choroidal neovascularization with no reduction or retardation in retinal vascular development and no retinal toxicity.

Conclusions: : Our data demonstrates that this novel HDAC inhibitor, HNHA, could be developed as a potential anti-angiogenic agent targeting HDAC to inhibit retinal and choroidal neovascularization.

Keywords: retinal neovascularization • choroid: neovascularization • neovascularization 
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