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Knockout of A 3 Adenosine Receptors Reduces Mouse Intraocular Pressure

By Mortimer M. Civan


PURPOSE. To test the putative role of A 3 adenosine receptors (ARs) in modulating intraocular pressure (IOP). METHODS. IOP was monitored for up to 32 minutes in A 3-knockout (A 3AR �/ � ) and A 3AR �/ � control mice by the servonull approach. The IOP responses to adenosine, A 3AR agonists and A 3AR antagonists were studied singly or in combination in both strains. RESULTS. IOP was significantly lower in A 3AR �/ � mice (12.9 � 0.7 mm Hg) than in A 3AR �/ � 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 A 3AR �/ � control mice (14.9 � 2.4 mm Hg). The A 3-selective agonist IB-MECA did not affect IOP in A 3-knockout mice, but raised it in A 3AR �/ � mice. The highly selective A 3AR antagonist MRS 1191 did not affect IOP in A 3AR �/ � mice, but lowered it in A 3AR �/ � control mice. Preadministering MRS 1191 did not affect the small adenosine-triggered increase in IOP in A 3AR �/ � mice, but markedly attenuated adenosine’s effects on IOP in A 3AR �/ � control mice. MRS 1523, an A 3AR antagonist less selective than MRS 1191 in rats, decreased IOP in both A 3AR �/ � and A 3AR �/ � 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 A 3AR �/ � and A 3AR �/ � mice. CONCLUSIONS. The reduced IOP and altered purinergic responses of IOP in A 3AR knockout mice support the conclusion that A 3ARs contribute to the regulation of IOP. (Invest Ophthalmo

Year: 2002
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