Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, USA.
Invest Ophthalmol Vis Sci. 2013 Jul 30;54(7):5103-10. doi: 10.1167/iovs.12-11491.
To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on IOP, mean arterial pressure (MAP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF), and outflow facility (OF) in monkeys.
Monkeys were treated with single or multiple topical treatments of 500 μg SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange.
Following four topical treatments with 500 μg SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10(-3) M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP.
Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.
确定一氧化氮供体硝普钠(SNP)和一氧化氮合酶(NOS)抑制剂 L-硝基精氨酸甲酯(L-NAME)对猴子眼压(IOP)、平均动脉压(MAP)、瞳孔直径(PD)、屈光度(Rfx)、房水形成(AHF)和流出道通畅性(OF)的影响。
猴子用单眼或双眼单次或多次局部滴注 500μg SNP 或 L-NAME 处理。用 Goldmann 压平眼压计测量 IOP,在室内光线下用游标卡尺测量 PD,用 Hartinger 符合折射计测量 Rx,用荧光光度法测量 AHF,用血压监测仪测量 MAP。用前房交换后的两级恒压灌注法测量 OF。
单次滴注 500μg SNP,间隔 30 分钟,共 4 次后,IOP 在 2 至 6 小时与对侧对照相比显著降低,IOP 在 3 小时时最大降低 20%(P<0.001)。PD、Rfx 和 AHF 均无变化。MAP 的影响是可变的。用 SNP 交换后,OF 增加 77%(P<0.05)。局部应用 L-NAME 对 IOP、PD、Rfx 或 MAP 均无影响。
在前节靶向组织中增加一氧化氮浓度可能是治疗青光眼降低眼压的一种有用方法。在得出关于 NOS 抑制对非人类灵长类动物眼生理影响的结论之前,还需要进行更多的研究。