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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To clarify the role of dysregulated purinergic signaling in pathogenesis of glaucoma.
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).
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.
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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