June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Sphingosine 1-phosphate elicits constriction of isolated porcine retinal arterioles
Author Affiliations & Notes
  • Takayuki Kamiya
    Asahikawa Medical University, Asahikawa, Japan
  • Taiji Nagaoka
    Asahikawa Medical University, Asahikawa, Japan
  • Tsuneaki Omae
    Asahikawa Medical University, Asahikawa, Japan
  • Shinji Ono
    Asahikawa Medical University, Asahikawa, Japan
  • Akitoshi Yoshida
    Asahikawa Medical University, Asahikawa, Japan
  • Footnotes
    Commercial Relationships Takayuki Kamiya, None; Taiji Nagaoka, None; Tsuneaki Omae, None; Shinji Ono, Kaken Pharmaceutical Co.,Ltd. (F); Akitoshi Yoshida, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4672. doi:
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    • Get Citation

      Takayuki Kamiya, Taiji Nagaoka, Tsuneaki Omae, Shinji Ono, Akitoshi Yoshida; Sphingosine 1-phosphate elicits constriction of isolated porcine retinal arterioles. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4672.

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

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Purpose: Sphingosine 1-phosphate (S1P), a member of a large family of lipid metabolites called sphingolipids, induces a wide variety of biologic responses, i.e., immune responses, inflammatory processes, organ perfusion, and regulation of vascular tone in different organs through various high-affinity G-protein-coupled receptors (S1PR) 1-5. However, few reports have addressed the effect of S1P on the retinal circulation. We examined the effect of S1P to determine the signaling mechanisms involved in the retinal microvasculature.

Methods: Porcine retinal arterioles (internal diameter, 70-100 µm) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record the changes in diameter in response to S1P.

Results: The retinal arterioles were constricted in a dose-dependent manner (1 nM-10 µM) in response to S1P. This vasoconstrictive response to S1P was not attenuated after removal of the endothelium. Blockade of S1PR2 by the S1PR2 antagonist JTE-013 abolished the vasoconstrictive response to S1P, whereas the S1PR1 antagonist (compound 5) and the S1PR3 antagonist (suramin) did not affect the vasoconstrictive response. The PKC inhibitor chelerythrine and store-operated calcium channels (SOCE) blocker (2-APB) significantly (p<0.0001) inhibited the effect of S1P-induced vasoconstriction.

Conclusions: S1P elicits vasoconstriction of the retinal arterioles via S1PR2. This vasoconstriction may be mediated by Ca2+-dependent and Ca2+-independent pathway.

Keywords: 688 retina • 499 diabetic retinopathy • 498 diabetes  

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