July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells
Author Affiliations & Notes
  • Ryo Terao
    University of Tokyo, Tokyo, Japan
    University of Tokyo, Tokyo, Japan
  • Makoto Aihara
    University of Tokyo, Tokyo, Japan
  • Footnotes
    Commercial Relationships   Ryo Terao, None; MEGUMI HONJO, None; Makoto Aihara, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3046. doi:
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      Ryo Terao, MEGUMI HONJO, Makoto Aihara; Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3046.

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

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Purpose : Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammatory responses and proangiogenic factors. It has been suggested that S1P upregulates choroidal neovascularization (CNV) and may be deeply involved in the pathogenesis of exudative age-related macular degeneration (AMD). In addition, recent studies have suggested that apolipoprotein M (ApoM), a carrier protein for S1P, modulates the biological properties of S1P in the pathogenesis of atherosclerosis. However, the role of ApoM/S1P in AMD has not been explored. We investigated the effect of S1P and ApoM on proangiogenic factors in vitro and in vivo.

Methods : The human RPE cell line ARPE-19 cells was used for the experiments. Cells were treated with exogenous S1P. The mRNA expression of vascular endothelial growth factor (VEGF) and protein level of Hypoxia inducible factor (HIF)-1α were evaluated. We also compared the expression of these factors and interleukin (IL)-8 in the presence of ApoM with albumin-bound S1P. In vivo, laser-induced murine model was generated to evaluate the progression of CNV formation. One eye was treated with intravitreal ApoM, and the other eye was treated with vehicle as a control.

Results : S1P promoted the expression of VEGF in RPE cells. HIF-1α expression was also upregulated. These S1P-induced enhancements in growth factors and IL-8 in RPE cells were significantly inhibited by ApoM treatment. Additionally, in vivo experiments using a laser-induced CNV murine model demonstrated that intravitreal ApoM injection significantly reduced the progression of CNV formation.

Conclusions : Although the detailed mechanisms remain to be elucidated, the present results provide a novel potential therapeutic target for AMD, and demonstrate a suppressive role for ApoM and S1P in the pathology of CNV progression.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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