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 P2Y1 (P2Y1R) and adenosine A1 receptors (A1AR), and of inositol-1,4,5-trisphosphate-receptor type 2 (IP3R2), 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 P2Y1R-/-, A1AR-/- and IP3R2-/- 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.

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