Dep. Bioquímica y Biología Molecular, Escuela Universitaria de Óptica, Universidad Complutense de Madrid, Spain.
Exp Eye Res. 2012 Aug;101:49-55. doi: 10.1016/j.exer.2012.05.011. Epub 2012 Jun 4.
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.
二核苷酸多聚磷酸、二磷酸肌苷(Ip(3)I)、二磷酸肌苷四钠(Ip(4)I)和二磷酸肌苷五钠(Ip(5)I)对新西兰白兔正常眼压的影响。Ip(5)I 可升高眼压,而 Ip(3)I 和 Ip(4)I 可降低眼压。Ip(4)I 是最有效的降低眼压诱导剂,与对照值相比,眼压最大下降 74.2±2.5%。剂量反应分析显示出浓度依赖性模式,pD(2)值为 6.19±0.18,相当于 EC(50)值为 0.63μM。关于 Ip(4)I 降低眼压的潜在机制,激动剂和拮抗剂的研究表明,Ip(4)I 通过眼部的 P2Y 受体降低眼压。我们认为,局部应用于角膜的 Ip(4)I 具有降低眼压的治疗潜力,眼压是青光眼的主要危险因素。