Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops
Reduction of Enhanced Rabbit Intraocular Pressure by Instillation of Pyroglutamic Acid Eye Drops
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DOI：
10.1248/bpb.b13-00159
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发表时间：
2013-06-01
影响因子：
2
通讯作者：
Tanaka, Ryuichiro
中科院分区：
文献类型：
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作者：
Ito, Yoshimasa;Nagai, Noriaki;Tanaka, Ryuichiro
l -焦谷氨酸（PGA）是由l -谷氨酸衍生的内源性分子。我们研究了PGA对实验性高眼压兔眼压（lOP）的影响。在体外和体内经角膜渗透研究中，PGA溶液（生理盐水中的PGA）没有穿透兔角膜。另一方面，氯化锌和2-羟丙基- β -环糊精（HPCD）的加入提高了PGA的穿透性，并且随着HPCD浓度的增加，PGA的穿透性增强。因此，本研究采用含有0.5%氯化锌和5%或10% HPCD （PGA/HPCD5%或10%滴眼液）的PGA溶液来研究对IOP的影响。通过耳缘静脉快速滴注5%葡萄糖溶液（15 mL/kg体重）或维持暗相5h，可引起IOP升高。在两种模型中，PGA/HPCD滴眼液均可阻止眼压升高，且眼压降低效果随滴眼液中HPCD浓度的增加而增强。注射5%葡萄糖溶液后，房水中一氧化氮（NO）水平升高，PGA/HPCD滴眼液也抑制了这种升高。综上所述，本研究表明PGA/HPCD滴眼液对实验性高眼压家兔具有降低眼压的作用，可能是由于抑制NO的产生。
L-Pyroglutamic acid (PGA) is an endogenous molecule derived from L-glutamate. We demonstrate the effects of PGA on intraocular pressure (lOP) in experimentally induced ocular hypertension in rabbits. In the in vitro and in vivo transcorneal penetration studies, the PGA solution (PGA in saline) did not penetrate the rabbit cornea. On the other hand, the penetration of PGA was improved by the addition of zinc chloride and 2-hydroxypropyl-beta-cyclodextrin (HPCD), and PGA penetration was enhanced with increasing HPCD concentration. Therefore, PGA solutions containing 0.5% zinc chloride and 5% or 10% HPCD (PGA/HPCD5% or 10% eye drops) were used to investigate the effects for IOP in this study. An elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 mL/kg of body weight) through the marginal ear vein or maintaining under dark phase for 5h. In the both models, the induced elevation in IOP was prevented by the instillation of PGA/HPCD eye drops, and the IOP-reducing effect enhanced with increasing HPCD concentration in the drops. Nitric oxide (NO) levels elevated in the aqueous humor following the infusion of 5% glucose solution, and this increase was also suppressed by the instillation of PGA/HPCD eye drops. In conclusion, the present study demonstrates that the instillation of PGA/HPCD eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably as a result of the suppression of NO production.