Identification of P2Y Receptor Subtypes in Human Müller Glial Cells by Physiology, Single Cell RT-PCR, and Immunohistochemistry

Fries, Julia E.; Goczalik, Iwona; Wheeler‐Schilling, Thomas H.; Köhler, Konrad; Guenther, Elke; Wolf, Sebastian; Wiedemann, Peter; Bringmann, Andreas; Reichenbach, Andreas; Francke, Mike; Pannicke, Thomas

doi:10.1167/iovs.05-0043

Cited by 46 publications

(17 citation statements)

References 53 publications

(56 reference statements)

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“…Indeed, in our hands, ATP was found to stimulate calcium influx in GS and GFAP-positive cells, possibly through ionotropic P 2 X 7 receptors, since these effects were blocked by brilliant blue G (not shown). Several purinergic ionotropic (Pannicke et al 2000) and metabotropic (Fries et al 2005) receptors have been identified in Müller glia and in retinal progenitors possibly mediating proliferation induced by ATP (Sholl-Franco et al 2010). Also, ATP is known to activate microglia in other areas of the CNS ).…”

Section: Discussionmentioning

confidence: 99%

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

et al. 2011

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Degeneration of neural retina causes vision impairment and can lead to blindness. Neural stem and progenitor cells might be used as a tool directed to regenerative medicine of the retina. Here, we describe a novel platform for cell phenotype-specific drug discovery and screening of proneurogenic factors, able to boost differentiation of neural retinal progenitor cells. By using single cell calcium imaging (SCCI) and a rational-based stimulation protocol, a diversity of cells emerging from differentiated retinal neurosphere cultures were identified. Exposure of retinal progenitor cultures to KCl or to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) stimulated Ca(2+) transients in microtubule-associated protein 2 (MAP-2) positive neurons. Doublecortin (DCX) and polysialated neural cell adhesion molecule (PSA-NCAM) positive neuroblasts were distinguished from differentiated neurons on the basis of their response to muscimol. Ca(2+) fluxes in glial fibrillary acidic protein (GFAP) or glutamine synthetase (GS) positive cells were induced by ATP. To validate the platform, neurospheres were treated with brain-derived neurotrophic factor (BDNF) (proneurogenic) or ciliary neurotrophic factor (CNTF) (gliogenic factor). BDNF increased the percentage of differentiated cells expressing Tuj-1 sensitive to KCl or AMPA and reduced the population of cells responding to muscimol. CNTF exposure resulted in a higher number of cells expressing GFAP responding to ATP. All together, our data may open new perspectives for cell type-specific discovery of drug targets and screening of novel proneurogenic factors to boost differentiation of neural retina cells to treat degenerative retinal diseases.

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Section: Discussionmentioning

confidence: 99%

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

et al. 2011

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“…Studies on the expression and function of P2Y receptors remain difficult due to limitations of available pharmacological tools and antibodies. Pharmacological experiments on M€ uller cell swelling (Uckermann et al, 2005;Wurm et al, 2008) and calcium imaging data (Li et al, 2001) indicate an expression of P2Y 1 in rat M€ uller cells; otherwise, several P2Y receptor subtypes have been found on tiger salamander (Reifel-Saltzberg et al, 2003) and human M€ uller cells (Fries et al, 2005), respectively. However, since most P2 receptor agonists and antagonists are rather unspecific, the interpretation of these data should be done with caution.…”

Section: Introductionmentioning

confidence: 99%

Expression and function of P2Y receptors on Müller cells of the postnatal rat retina

Wurm

Erdmann

Bringmann

et al. 2009

Glia

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In the postnatal and mature retina, many processes are controlled by the action of nucleotides. Their effects are partly mediated via activation of metabotropic P2Y receptors. However, little is known about the developmental regulation and cellular localization of P2Y receptor subtypes. Combining immunohistochemical and neurophysiological methods, we investigated the developmental expression of P2Y receptors on Müller cells, the principal macroglial cells of the retina. The P2Y(1) and the P2Y(4) receptors, but no other subtypes, were unequivocally localized on Müller cells. P2Y(1) was expressed from postnatal day 5 (P5) on and mediated a calcium response to ATP in Müller cells as well as a volume regulatory signaling cascade preventing Müller cells from swelling under hypotonic conditions. Differentiation of Müller cells was accompanied by a change of the calcium response pattern; the calcium responses in Müller cell endfeet persisted, but ATP responsiveness of Müller cell somata disappeared. P2Y(4) immunoreactivity was observed in Müller cell endfeet and synaptic terminals of rod bipolar cells from P20 on. Activated protein kinases were detected by immunohistochemistry; p-ERK occurred in Müller cells and amacrine cells, whereas p-Akt was detected in bipolar cells. Our data indicate that purinergic signaling via P2Y(1) and P2Y(4) receptors might contribute to differentiation processes in the postnatal retina.

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“…P2Y1 receptor has been reported to be expressed in the retina of rat [8,11,12], developing chick embryo [13], and human glial cells [10]. However, little information is available to understand the role of P2Y1 activation not only for physiologic action but also for tumorigenesis in retinoblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Expression profiles and physiological characteristics of P2Y receptors have been investigated in various retinal tissues. Several subtypes of P2Y receptors, including P2Y1, P2Y2, P2Y4, and P2Y6, are expressed in retinal neurons and glial cells [8,[10][11][12][13]. Particularly, P2Y2 receptor mRNA has been verified in the ganglion cell layer and the inner nuclear layer of adult Rhesis Macaques and albino rabbits [9].…”

Section: Introductionmentioning

confidence: 97%

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Functional Expression of P2Y Receptors in WERI-Rb1 Retinoblastoma Cells

Kim

Park

Sohn

et al. 2011

Korean J Physiol Pharmacol

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Identification of P2Y Receptor Subtypes in Human Müller Glial Cells by Physiology, Single Cell RT-PCR, and Immunohistochemistry

Abstract: The presented data obtained by different techniques revealed that human Müller cells express P2Y1, P2Y2, P2Y4, and P2Y6 receptors. The specific roles of these receptor subtypes in retinal physiology and/or pathophysiology remain to be investigated in future studies.

Cited by 46 publications

References 53 publications

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

Expression and function of P2Y receptors on Müller cells of the postnatal rat retina

Functional Expression of P2Y Receptors in WERI-Rb1 Retinoblastoma Cells

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