College of Optometry, University of Houston, 505 J. Davis Armistead Building, Houston, TX 77204, USA.
Exp Eye Res. 2010 May;90(5):605-16. doi: 10.1016/j.exer.2010.02.005. Epub 2010 Feb 14.
Many studies have used pilocarpine to stimulate accommodation in both humans and monkeys. However, the concentrations of pilocarpine used and the methods of administration vary. In this study, three different methods of pilocarpine administration are evaluated for their effectiveness in stimulating accommodation in rhesus monkeys. Experiments were performed in 17 iridectomized, anesthetized rhesus monkeys aged 4-16 years. Maximum accommodation was stimulated in all these monkeys with a 2% pilocarpine solution maintained on the cornea for at least 30 min in a specially designed perfusion lens. In subsequent topical pilocarpine experiments, baseline refraction was measured with a Hartinger coincidence refractometer and then while the monkeys were upright and facing forward, commercially available pilocarpine (2, 4, or 6%) was applied topically to the cornea as 2 or 4 drops in two applications or 6 drops in three applications over a five minute period with the eyelids closed between applications. Alternatively, while supine, 10-12 drops of pilocarpine were maintained on the cornea in a scleral cup for 5 min. Refraction measurements were begun 5 min after the second application of pilocarpine and continued for at least 30 min after initial administration until no further change in refraction occurred. In intravenous experiments, pilocarpine was given either as boluses ranging from 0.1mg/kg to 2mg/kg or boluses followed by a constant infusion at rates between 3.06 mg/kg/h and 11.6 mg/kg/h. Constant 2% pilocarpine solution on the eye in the perfusion lens produced 10.88+/-2.73 D (mean+/-SD) of accommodation. Topically applied pilocarpine produced 3.81 D+/-2.41, 5.49 D+/-4.08, and 5.55 D+/-3.27 using 2%, 4%, and 6% solutions respectively. When expressed as a percentage of the accommodative response amplitude obtained in the same monkey with constant 2% pilocarpine solution on the eye, the responses were 34.7% for 2% pilocarpine, 48.4% for 4% pilocarpine, and 44.6% for 6% pilocarpine. Topical 4% and 6% pilocarpine achieved similar, variable accommodative responses, but neither achieved maximum accommodation. IV boluses of pilocarpine achieved near maximal levels of accommodation at least ten times faster than topical methods. Doses effective for producing maximum accommodation ranged from 0.25mg/kg to 1.0mg/kg. IV pilocarpine boluses caused an anterior movement of the anterior lens surface, a posterior movement of the posterior lens surface, and a slight net anterior movement of the entire lens. Considerable variability in response amplitude occurred and maximum accommodative amplitude was rarely achieved with topical application of a variety of concentrations of commercially available pilocarpine. Intravenous infusion of pilocarpine was a rapid and reliable method of producing a nearly maximal accommodative response and maintaining accommodation when desired.
许多研究已经使用毛果芸香碱来刺激人类和猴子的调节。然而,使用的毛果芸香碱浓度和给药方法各不相同。在这项研究中,评估了三种不同的毛果芸香碱给药方法在刺激恒河猴调节中的有效性。在 17 只虹膜切除、麻醉的 4-16 岁恒河猴中进行了实验。所有这些猴子都用 2%的毛果芸香碱溶液在角膜上保持至少 30 分钟,以刺激最大调节,这种溶液是在专门设计的灌注透镜中使用的。在随后的局部毛果芸香碱实验中,用哈廷格符合折射计测量基础屈光度,然后在猴子直立向前看时,将市售的毛果芸香碱(2%、4%或 6%)以 2 或 4 滴分 2 次应用或 6 滴分 3 次应用,每次间隔 5 分钟,同时闭眼。或者,在仰卧位时,用巩膜杯将 10-12 滴毛果芸香碱保持在角膜上 5 分钟。在第二次应用毛果芸香碱后 5 分钟开始进行折射测量,并在初始给药后至少 30 分钟继续进行,直到折射不再发生变化。在静脉内实验中,毛果芸香碱以 0.1mg/kg 至 2mg/kg 的剂量或剂量后以 3.06mg/kg/h 至 11.6mg/kg/h 的恒速输注给予。在灌注透镜中,眼内的恒速 2%毛果芸香碱溶液产生 10.88+/-2.73 D(均值+/-标准差)的调节。局部应用的毛果芸香碱分别产生 3.81 D+/-2.41、5.49 D+/-4.08 和 5.55 D+/-3.27,使用的浓度分别为 2%、4%和 6%。当以在同一只猴子的眼内用恒速 2%毛果芸香碱溶液获得的调节反应幅度的百分比表示时,2%毛果芸香碱的反应为 34.7%,4%毛果芸香碱为 48.4%,6%毛果芸香碱为 44.6%。局部应用 4%和 6%的毛果芸香碱产生相似的、可变化的调节反应,但均未达到最大调节。静脉内毛果芸香碱推注比局部方法快至少 10 倍达到接近最大的调节水平。产生最大调节所需的有效剂量范围为 0.25mg/kg 至 1.0mg/kg。静脉内毛果芸香碱推注导致前晶状体表面向前移动,后晶状体表面向后移动,整个晶状体轻微向前净移动。反应幅度的变化相当大,并且用市售的各种浓度的毛果芸香碱进行局部应用很少能达到最大的调节幅度。静脉内输注毛果芸香碱是一种快速可靠的方法,可产生几乎最大的调节反应,并在需要时维持调节。