June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Dysregulation in purinergic signaling causes hypertensive glaucoma-like optic neuropathy
Author Affiliations & Notes
  • Youichi Shinozaki
    Neuropharmacology, University of Yamanashi, Chuo, Japan
  • Kenji Kashiwagi
    Department of Ophthalmology, University of Yamanashi, Yamanashi, Japan
  • Akiko Takeda
    Neuropharmacology, University of Yamanashi, Chuo, Japan
  • Nobuhiko Ohno
    Natl Inst Physiol Sci, Aichi, Japan
  • Schuichi Koizumi
    Neuropharmacology, University of Yamanashi, Chuo, Japan
  • Footnotes
    Commercial Relationships   Youichi Shinozaki, University of Yamanashi (P); Kenji Kashiwagi, University of Yamanashi (P); Akiko Takeda, None; Nobuhiko Ohno, None; Schuichi Koizumi, University of Yamanashi (P)
  • Footnotes
    Support  JSPS KAKENHI Grant JP16K18390, JP16H06280 and Takeda Science Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2550. doi:
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      Youichi Shinozaki, Kenji Kashiwagi, Akiko Takeda, Nobuhiko Ohno, Schuichi Koizumi; Dysregulation in purinergic signaling causes hypertensive glaucoma-like optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2550.

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

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Abstract

Purpose : To clarify the role of dysregulated purinergic signaling in pathogenesis of glaucoma.

Methods : Experiments were performed using C57BL/6 (wild type, WT) and P2Y6 receptor knockout (P2Y6KO) mice. Intraocular pressure (IOP) was measured using rebound tonometer (Tonolab). Fluorophotometric analysis was performed by application of sodium fluorescein and eyes were monitored using LAS4000. The number of retinal ganglion cells (RGCs) in the whole mount retina was estimated by labelling of these cells with anti-Brn3a antibody. For detailed analysis of optic nerve, we used Serial block-face scanning electron microscopy (SBF-SEM).

Results : Instillation of UDP, selective agonist for P2Y6 receptor, reduced IOP in WT mice in a concentration-dependent manner. Its effect was transient and the maximum effect was obtained at 1.5 h after application. MRS2578, selective antagonist for P2Y6 receptor, increased IOP in WT mice. Hypotensive effect of UDP was disappeared in P2Y6KO mice. P2Y6 receptor was expressed in non-pigmented epithelial (NPE) cells of ciliary body. Fluorophotometric analysis showed UDP changes aqueous humor (AH) dynamics. P2Y6KO mice showed sustained IOP elevation and reduction in RGC number in an age-dependent manner. WT mice showed no significant changes in RGC number regardless of their age. Chronic suppression of elevated IOP in P2Y6KO mice by daily application of latanoprost for more than 4 months rescued RGC number. SBF-SEM demonstrated axonal abnormalities in aged P2Y6KO mice but not young ones.

Conclusions : These data suggest that UDP reduces IOP via controlling AH dynamics and dysregulation in P2Y6R signaling causes hypertensive glaucoma-like phenotype in mice.

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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