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Abstract #65943 Published in IGR 17-3
Müller cell-mediated neurite outgrowth of the retinal ganglion cells via P2Y6 receptor signals
Taguchi M; Shinozaki Y; Kashiwagi K; Shigetomi E; Robaye B; Koizumi SJournal of Neurochemistry 2015; 0:
Müller cells, the primary macroglia of the retina, support various functions of retinal ganglion cells (RGCs). Here, we demonstrate a nucleotide-mediated communication between these two types of cells, by which Müller cells control neurite outgrowth of RGCs by activation of P2 receptors such as P2Y6 . Cultured mouse RGCs had significantly enhanced neurite outgrowth when cultured with either cultured mouse Müller cells or conditioned medium derived from Müller cells, and this was completely inhibited by the nucleotide-degrading enzyme, apyrase. This increase in outgrowth was mimicked by exogenously applied nucleotides such as ATP, UTP and UDP. Pharmacological and genetic analysis revealed that P2Y6 receptor in RGCs was responsible for the increased neurite outgrowth. P2Y6 receptor was expressed in the ganglion cell layer of the retina and in RGC primary cultures. High performance liquid chromatography has revealed that Müller cells constitutively release UTP, which is immediately metabolized into UDP, an endogenous agonist for P2Y6 receptor. In the in vitro ocular hypertension model (i.e. glaucoma model), neurite outgrowth in RGCs was significantly reduced, which was associated with a decrease in P2Y6 receptors. Taken together, Müller cells control neurite outgrowth of RGCs by activating P2 receptors such as P2Y6 receptor, and the receptor expression level might be down-regulated in glaucoma. This article is protected by copyright. All rights reserved.
Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Full articleClassification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)