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

Abstract

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.

Involvement of nucleotides in glial growth following scratch injury in avian retinal cell monolayer cultures

“…*p<0.05 and **p<0.01 compared to control. Bar=20 μm ADP-sensitive P2Y 1 receptors were previously described in Müller glial cells [22], a finding that is corroborated by our present observation that ADP induces intracellular calcium increases in Müller cells growing at the edge of the scratch in the cultures. Moreover, although MRS2179, a specific antagonist of P2Y 1 receptors, significantly decreased ADPinduced proliferation of glial progenitors in early developing retinal cultures, this compound did not affect the growth of glia in the scratched cultures, reinforcing our hypothesis that UTP preferring P2Y 2 /P2Y 4 receptors are the sites involved in the growth of glia to the scratched area.…”

“…Finally, although Muller cells from adult human and rat retinas express transcripts for both P2Y 2 and P2Y 4 receptors [17], only immunoreactivity for the P2Y 4 receptor protein was detected in Muller cells from the rodent retina [22], suggesting that these cells express only the P2Y 4 UTP-sensitive receptor subtype. In the present work, we detected the P2Y 2 receptor protein with an antiserum against the rat P2Y 2 receptor in extracts from purified chick retinal glial cultures.…”

“…During development, evidence for the presence of P2Y 1 receptors in glial progenitors was obtained in chick embryo retinal cultures and early postnatal rodent retina [20][21][22][23]. Activation of these receptors by ATP or ADP induces the proliferation of glial progenitors by a mechanism involving PKC, MAPK, and PI3K/AKT pathways [23][24][25][26].…”

Subcellular propagation of calcium waves in Müller glia does not require autocrine/paracrine purinergic signaling

“…Given that previous studies in human M€ uller glia showed ionotropic P 2 X-mediated components, [27][28] we tested whether P 2 X receptors might contribute to the [Ca 2C ] i response associated with SOCE. Activity of the P 2 Y-IP 3 pathway was minimized by blocking Ca 2C flux through intracellular release channels with the SERCA (sarcoplasmic endoplasmic reticulum Ca 2C ATPase) antagonist cyclopiazonic acid (CPA; 5 mM).…”

NTPDase2 and the P2Y1 receptor are not required for mammalian eye formation

“…P2Y 1 receptors are the principal receptors on Müller glial cells [25], but they are also expressed by cholinergic amacrine cells [26]. It has previously been shown that ATP stimulates proliferation of neural retinal progenitor cells in the embryonic chicken retina [27,28].…”