Disruption of endogenous purinergic signaling inhibits vascular endothelial growth factor- and glutamate-induced osmotic volume regulation of müller glial cells in knockout mice

Abstract

Background/Aims: Osmotic swelling of Müller cells is a common phenomenon in animal models of ischemic and diabetic retinopathies. Müller cells possess a swelling-inhibitory purinergic signaling cascade which can be activated by various receptor ligands including vascular endothelial growth factor (VEGF) and glutamate. Here, we investigated whether deletion of P2Y 1 (P2Y1R) and adenosine A1 receptors (A 1AR), and of inositol-1,4,5-trisphosphate-receptor type 2 (IP 3R2), in mice affects the inhibitory action of VEGF and glutamate on Müller cell swelling. Methods: The cross-sectional area of Müller cell somata was recorded after a 4-min superfusion of retinal slices with a hypoosmotic solution. Results: Hypoosmolarity induced a swelling of Müller cells from P2Y1R-/-, A1AR-/- and IP3R2-/- mice, but not from wild-type mice. Swelling of wild-type Müller cells was induced by hypoosmotic solution containing barium chloride. Whereas VEGF inhibited the swelling of wild-type Müller cells, it had no swelling-inhibitory effect in cells from A1AR -/- and IP3R2-/- mice. Glutamate inhibited the swelling of wild-type Müller cells but not of cells from P2Y 1R-/-, A1AR-/- and IP 3R2-/- animals. Conclusion: The swelling-inhibitory effects of VEGF and glutamate in murine Müller cells is mediated by transactivation of P2Y1R and A1AR, as well as by intracellular calcium signaling via activation of IP3R2. Copyright © 2013 S. Karger AG, Basel.