June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
CD200 Receptor signaling subverts pro-angiogenic macrophage phenotype generation and experimental chorioretinal neovascularisation
Author Affiliations & Notes
  • Shintaro Horie
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • David Copland
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Jian Liu
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Wei-Kang Wu
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Lindsay Nicholson
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Manabu Mochizuki
    Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Andrew Dick
    Department of Academic Unit of Ophthalmology, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Footnotes
    Commercial Relationships Shintaro Horie, None; David Copland, None; Jian Liu, None; Wei-Kang Wu, None; Lindsay Nicholson, None; Manabu Mochizuki, Santen (F), Senju (F), Ohtsuka (F), Daiichi-Sankyo (F), Mitsubishi-Tanabe (F), AMO Japan (F), Alcon Japan (F); Andrew Dick, Novartis (C), Novartis (F), GSK (F), Abbott (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 155. doi:
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      Shintaro Horie, David Copland, Jian Liu, Wei-Kang Wu, Lindsay Nicholson, Manabu Mochizuki, Andrew Dick; CD200 Receptor signaling subverts pro-angiogenic macrophage phenotype generation and experimental chorioretinal neovascularisation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):155.

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

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Abstract

Purpose: To investigate how CD200R signaling regulates PGE2-mediated modulation of macrophage phenotype and function in the suppression of angiogenesis.

Methods: Bone marrow derived macrophages (BMMφ) were generated from wild-type C57BL/6 (WT) or CD200R1-/- mice. For in vitro assays, BMMφ were stimulated with purified Prostaglandin E2 (PGE2) or supernatant from conditioned murine RPE cell line, and cell phenotype and pro-angiogenic function assessed by quantitative RT-PCR, ELISA and immuno-cytochemistry. Assessment of angiogenic potential was performed in vitro, using the endothelial tube formation assay from human umbilical vein endothelial cells (HUVECs) in co-culture with conditioned BMMφ, and in vivo using a laser-induced choroidal neovascularization (CNV) model. Operative PGE2-signaling pathways (including MAPK) were analyzed by flow cytometry.

Results: BMMφ from CD200R1-/- mice expressed increased Vegf-a mRNA and secreted higher amounts of VEGF protein following PGE2-stimulation when compared to WT cells. Similar levels of expression were observed when BMMφ were cultured with conditioned RPE cell supernatant. The formation of endothelial tubes by HUVECs was promoted when co-cultured with PGE2 or RPE-conditioned CD200R1-/- BMMφ. In vivo assessment demonstrated increased CNV area in CD200R1-/- as compared to WT mice. Furthermore, PGE2-stimulation lead to up-regulation of phosphorylated MAPK in CD200R1-/- BMMφ.

Conclusions: In the absence of inhibitory CD200R signaling, VEGF expression from macrophages is elevated, which results in an increased pro-angiogenic potential in HUVECs co-culture, and increased area of laser-induced CNV. Furthermore, this data shows that CD200R suppression of PGE2-mediated myeloid-induced VEGF expression, in part is due to inhibition of MAPK pathway, and demonstrates the anti-angiogenic function of myeloid CD200R signaling.

Keywords: 555 immunomodulation/immunoregulation • 609 neovascularization  
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