June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
The role of a novel regulator of Wnt signalling in ocular angiogenesis
Author Affiliations & Notes
  • Beiying Qiu
    Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
  • Alison Tan
    Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
  • Veluchamy A Barathi
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • Sze Yuan Ho
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  • Zhou Lei
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • Ning Cheung
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • Gemmy Cheung
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • Tien Yin Wong
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
    Ophthalmology & Visual Sciences Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore
  • Wanjin Hong
    Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  • Xiaomeng Wang
    Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
  • Footnotes
    Commercial Relationships   Beiying Qiu, None; Alison Tan, None; Veluchamy Barathi, None; Sze Yuan Ho, None; Zhou Lei, None; Ning Cheung, None; Gemmy Cheung, Bayer (C), Bayer (F), GlaxoSmithKline (F), Novartis (C), Novartis (F), Roche (F); Tien Wong, Abbott (C), Abbott (F), Allergan (C), Allergan (F), Bayer (C), Bayer (F), Genentech (C), Genentech (F), Novartis (C), Novartis (F), Pfizer (C), Pfizer (F), Roche (C), Roche (F); Wanjin Hong, None; Xiaomeng Wang, None
  • Footnotes
    Support  Singapore Biomedical Research Council-Strategic Positioning Fund (Ref No. SPF 2014/002: SIPRAD)
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4443. doi:
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      Beiying Qiu, Alison Tan, Veluchamy A Barathi, Sze Yuan Ho, Zhou Lei, Ning Cheung, Gemmy Cheung, Tien Yin Wong, Wanjin Hong, Xiaomeng Wang; The role of a novel regulator of Wnt signalling in ocular angiogenesis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4443.

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

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Abstract

Purpose : Abnormal blood vessel formation is a hallmark of many blinding eye diseases, including proliferative diabetic retinopathy (PDR) and age-related macular degeneration (AMD). Our previous study showed a reduced expression level of a secreted frizzled related protein (SFRP) in vitreous of PDR patients as compared to that in control patients. The purpose of this study is to investigate the role of this SFRP in retinal vascular cell function and angiogenesis.

Methods : Recombinant human SFRP Fc chimera protein was generated and purified before being tested for its impact on human retinal endothelial cell (HREC) proliferation, ability to form tube like structure, and monocyte recruitment. Ex vivo assays including Choroid sprouting assay, aortic ring assay and metatarsal assay were used to study the impact of SFRP-Fc as well as N-terminal domain (SFRP-N-Fc) and C-terminal domain (SFRP-C-Fc) on angiogenesis. SFRP-Fc and SFRP-C-Fc were further evaluated in a mouse model of laser-induced choroidal neovascularization (CNV) and a rabbit model of persistent retinal neovascularization (PRNV).

Results : Our study demonstrated a strong inhibitory effect of SFRP on HREC proliferation, tube formation and monocyte adhesion. We further showed that the C-terminal domain of HREC is responsible for its anti-angiogenic function. Both SFRP-Fc and SFRP-C-Fc are able to inhibits vessel outgrowth as demonstrated in multiple ex vivo assays. Finally, our study revealed a potent anti-angiogenic effect of SFRP-Fc and SFRP-C-Fc in mouse model of laser-induced CNV and in rabbit model of PRNV.

Conclusions : This study revealed SFRP as a potent anti-angiogenic factor and its functional domain is located at the C-terminal region domain of the SFRP protein.

This is a 2020 ARVO Annual Meeting abstract.

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