June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Efficacy of a marine natural product on experimental ocular angiogenesis
Author Affiliations & Notes
  • Xiaomeng Wang
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Beiying Qiu
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Raj Patil
    ratina , Singapore Eye Research Institurte, Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore, Singapore
  • Veluchamy A Barathi
    Translational Preclincal Model, Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore, Singapore
  • Walter Hunziker
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Hendrik Luesch
    College of Pharmacy, University of Florida, Gainesville, Florida, United States
    Oceanyx Pharmaceuticals, Inc., Alachua, Florida, United States
  • Tien Yin Wong
    Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore, Singapore
  • Wanjin Hong
    Institute of Molecular and Cell Biology, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Xiaomeng Wang, None; Beiying Qiu, None; Raj Patil, None; Veluchamy Barathi, None; Walter Hunziker, None; Hendrik Luesch, Oceanyx Pharmaceuticals (F), Oceanyx Pharmaceuticals (I), Oceanyx Pharmaceuticals (E), Oceanyx Pharmaceuticals (C), Oceanyx Pharmaceuticals (P); Tien Wong, None; Wanjin Hong, None
  • Footnotes
    Support  The work is supported by SIPRAD and Singapore BMRC, A*STAR
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4080. doi:
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    • Get Citation

      Xiaomeng Wang, Beiying Qiu, Raj Patil, Veluchamy A Barathi, Walter Hunziker, Hendrik Luesch, Tien Yin Wong, Wanjin Hong; Efficacy of a marine natural product on experimental ocular angiogenesis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4080.

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

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Abstract

Purpose : A subset of patients with retinal angiogenic disease such as diabetic retinopathy do not respond or respond poorly to anti-VEGF agents, and targeting alternative mechanisms of angiogenesis, possibly in combination with anti-VEGF agents, is a major goal in ocular angiogenesis research. We investigated the impact of a marine natural product, SIPRAD0279, which was modified for reduced toxicity, on experimental ocular angiogenesis.

Methods : The effect of SIPRAD0279 on angiogenesis was studied using ex vivo and in vivo angiogenesis assays, including choroid and metatarsal sprouting assays, aortic ring assay and in the mouse model of oxygen induced retinopathy (OIR). After the treatment with SIPRAD0279, organ explants and retina flatmounts were subjected to immunofluorescence staining with vascular markers for quantitative analysis of blood vessel formation.

Results : SIPRAD0279 completely blocked vessel outgrowth from choroid, metatarsal and aortic explants at 300pM with IC50=130.5±22 pM. Interestingly, SIPRAD0279 had no impact on preformed choroidal vasculature at this dosage. In the mouse model of OIR, intraperitoneal injection of 0.25 mg/kg SIPRAD0279 caused significant inhibition on pathological neovascularization without affecting physiological blood vessel re-growth in the retina.

Conclusions : Our study demonstrates that a modified marine natural product (SIPRAD0279) is a potent angiogenic inhibitor that selectively inhibits pathological neovascularization in the retina and not choroid. SIPRAD0279 could be further developed as an alternative treatment strategy for ocular diseases such as proliferative diabetic retinopathy.

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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