The ability of diinosine polyphosphates, diinosine triphosphate (Ip(3)I), diinosine tetraphosphate (Ip(4)I) and diinosine pentaphosphate (Ip(5)I) to modify intraocular pressure in normotensive New Zealand white rabbits was tested. Ip(5)I produced increase in intraocular pressure, while Ip(3)I and Ip(4)I produced a decrease. Ip(4)I was the most effective reducing intraocular pressure inducing a maximal decrease of intraocular pressure to 74.2 ± 2.5% compared with the control value. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD(2) value of 6.19 ± 0.18, equivalent to an EC(50) of 0.63 μM. Regarding the underlying mechanism used by Ip(4)I to reduce intraocular pressure, studies with agonists and antagonists revealed that Ip(4)I reduces intraocular pressure via P2Y receptors in the eye. We suggest that topical application of Ip(4)I to the cornea has therapeutic potential for lowering intraocular pressure, a major risk factor for glaucoma.
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