Involvement of A1 adenosine receptors in osmotic volume regulation of retinal glial cells in mice

Purpose: Osmotic swelling of Muller glial cells has been suggested to contribute to retinal edema. We determined the role of adenosine signaling in the inhibition of Muller cell swelling in the murine retina. Methods: The size of Muller cell somata was recorded before and during perfusion of retinal sections and isolated Muller cells with a hypoosmolar solution. Retinal tissues were freshly isolated from wild-type mice and mice deficient in A(1) adenosine receptors (A(1)AR(-/-)), or cultured as whole-mounts for three days. The potassium conductance of Muller cells was recorded in isolated cells, and retinal slices were immunostained against Kir4.1. Results: Hypotonic exposure for 4 min induced a swelling of Muller cell bodies in retinal slices from A(1)AR(-/-) mice but not wild-type mice. Pharmacological inhibition of A(1) receptors or of the ecto-5'-nucleotidase induced hypoosmotic swelling of Muller cells from wild-type mice. Exogenous adenosine prevented the swelling of Muller cells from wildtype but not A(1)AR(-/-) mice. The antiinflammatory corticosteroid, triamcinolone acetonide, inhibited the swelling of Muller cells from wild-type mice; this effect was blocked by an antagonist of A(1) receptors. The potassium conductance of Muller cells and the Kir4.1 immunolabeling of retinal slices were not different between A(1)AR(-/-) and wild-type mice, both in freshly isolated tissues and retinal organ cultures. Conclusions: The data suggest that autocrine activation of A(1) receptors by extracellularly generated adenosine mediates the volume homeostasis of Muller cells in the murine retina. The swelling-inhibitory effect of triamcinolone is mediated by enhancement of endogenous adenosine signaling.