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Marcel Y. Avila, Richard A. Stone, Mortimer M. Civan; Knockout of A3 Adenosine Receptors Reduces Mouse Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2002;43(9):3021-3026.
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purpose. To test the putative role of A3 adenosine receptors (ARs) in modulating intraocular pressure (IOP).
methods. IOP was monitored for up to 32 minutes in A3-knockout (A3AR−/−) and A3AR+/+ control mice by the servo-null approach. The IOP responses to adenosine, A3AR agonists and A3AR antagonists were studied singly or in combination in both strains.
results. IOP was significantly lower in A3AR−/− mice (12.9 ± 0.7 mm Hg) than in A3AR+/+ control animals (17.4 ± 0.6 mm Hg). The nonselective AR agonist adenosine produced a much smaller increase in IOP (2.2 ± 0.8 mm Hg) in the knockout than in A3AR+/+ control mice (14.9 ± 2.4 mm Hg). The A3-selective agonist IB-MECA did not affect IOP in A3-knockout mice, but raised it in A3AR+/+ mice. The highly selective A3AR antagonist MRS 1191 did not affect IOP in A3AR−/− mice, but lowered it in A3AR+/+ control mice. Preadministering MRS 1191 did not affect the small adenosine-triggered increase in IOP in A3AR−/− mice, but markedly attenuated adenosine’s effects on IOP in A3AR+/+ control mice. MRS 1523, an A3AR antagonist less selective than MRS 1191 in rats, decreased IOP in both A3AR−/− and A3AR+/+ animals. As in black Swiss outbred mice and other mammalian species, reducing aqueous humor inflow with acetazolamide lowered IOP and administering water intraperitoneally increased IOP in both A3AR−/− and A3AR+/+ mice.
conclusions. The reduced IOP and altered purinergic responses of IOP in A3AR knockout mice support the conclusion that A3ARs contribute to the regulation of IOP.
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