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

[摘要] Purpose: Osmotic swelling of Müllerglial cells has been suggested to contribute to retinal edema. Wedetermined the role of adenosine signaling in the inhibition of Müllercell swelling in the murine retina. Methods: The size of Müller cell somatawas recorded before and during perfusion of retinal sections andisolated Müller cells with a hypoosmolar solution. Retinal tissues werefreshly isolated from wild-type mice and mice deficient in A1adenosine receptors (A1AR−/−), or culturedas whole-mounts for three days. The potassium conductance of Müllercells was recorded in isolated cells, and retinal slices wereimmunostained against Kir4.1. Results: Hypotonic exposure for 4 mininduced a swelling of Müller cell bodies in retinal slices from A1AR−/−mice but not wild-type mice. Pharmacological inhibition of A1receptors or of the ecto-5′-nucleotidase induced hypoosmotic swellingof Müller cells from wild-type mice. Exogenous adenosine prevented theswelling of Müller cells from wild-type but not A1AR−/−mice. The antiinflammatory corticosteroid, triamcinolone acetonide,inhibited the swelling of Müller cells from wild-type mice; this effectwas blocked by an antagonist of A1 receptors. The potassiumconductance of Müller cells and the Kir4.1 immunolabeling of retinalslices were not different between A1AR−/−and wild-type mice, both in freshly isolated tissues and retinal organcultures. Conclusions: The data suggest thatautocrine activation of A1 receptors by extracellularlygenerated adenosine mediates the volume homeostasis of Müller cells inthe murine retina. The swelling-inhibitory effect of triamcinolone ismediated by enhancement of endogenous adenosine signaling.

[学科分类] 生物化学/生物物理