June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Characterization of anti-angiogenic properties of histone deacetylase (HDAC) inhibitor from marine bacteria in human retinal vascular endothelial cells
Author Affiliations & Notes
  • Wei Cheng
    SIPRAD, Institute of Molecular and Cell Biology, Singapore, Singapore
  • Queenie Tan
    SIPRAD, Institute of Molecular and Cell Biology, Singapore, Singapore
  • Raj Patil
    Retina, Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology & Visuals Sciences ACP, Duke NUS Medical School, Singapore, Singapore
  • Walter Hunziker
    SIPRAD, Institute of Molecular and Cell Biology, Singapore, Singapore
  • Hendrik Luesch
    Oceanyx Pharmaceuticals, Alachua, Florida, United States
    College of Pharmacy, University of Florida, Gainesville, Florida, United States
  • Tien Yin Wong
    Retina, Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology & Visuals Sciences ACP, Duke NUS Medical School, Singapore, Singapore
  • Wanjin Hong
    SIPRAD, Institute of Molecular and Cell Biology, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Wei Cheng, None; Queenie Tan, None; Raj Patil, None; Walter Hunziker, None; Hendrik Luesch, Oceanyx Pharmaceuticals (F), Oceanyx Pharmaceuticals (I), Oceanyx Pharmaceuticals (E), Oceanyx Pharmaceuticals (P), Oceanyx Pharmaceuticals (S); Tien Yin Wong, None; Wanjin Hong, None
  • Footnotes
    Support  SERI-IMCB Program in Retinal Angiogenic Diseases (SIPRAD) and Singapore BMRC, A*STAR
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1927. doi:
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      Wei Cheng, Queenie Tan, Raj Patil, Walter Hunziker, Hendrik Luesch, Tien Yin Wong, Wanjin Hong; Characterization of anti-angiogenic properties of histone deacetylase (HDAC) inhibitor from marine bacteria in human retinal vascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1927.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) and proliferative diabetic retinopathy are the leading causes of blindness worldwide. Pathological angiogenesis of the retina is an important process involved in these eye diseases. Since significant number of patients do not respond to the current therapy, the need to discover new targets is high. We investigated here role of SIPRAD0280, a histone deacetylase (HDAC) inhibitor isolated from marine bacteria, on retinal angiogenesis.

Methods : In vitro angiogenesis assays such as cell proliferation, transwell migration and tube formation were performed using primary human retinal microvascular endothelial to evaluate the efficacy of HDAC inhibitor (SIPRAD0280) on retinal angiogenesis. VEGF165 and Linifanib, a potent inhibitor of RTK were used as the reference compounds.

Results : SIPRAD0280 inhibited VEGF or non-VEGF induced endothelial cells proliferation in a dose dependent manner. The VEGF induced proliferation and cell migration was reduced by 48.2 ± 11.4% (n =5) and 93.4 ± 1.6% (n =3), respectively in the presence of 100 nM SIPRAD0280. SIPRAD0280 also inhibited basal migration by 76.4 ± 5.7% (n =3). Further, SIPRAD0280 completely blocked the retinal endothelial cells tube formation at 10 nM.

Conclusions : Our results demonstrate that histone deacetylase (HDAC) inhibitor, SIPRAD0280, significantly impaired the angiogenic processes in a dose dependent manner in human retinal endothelial cells. SIPRAD0280 has a potential be developed as a druggable small molecule inhibitor for the modulation of neovascularization in ocular diseases.

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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