局部用拉坦前列素对兔、猴和人类视神经乳头循环的影响。

Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans.

作者信息

Ishii K, Tomidokoro A, Nagahara M, Tamaki Y, Kanno M, Fukaya Y, Araie M

机构信息

Eye Clinic, Omiya Red Cross Hospital, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2001 Nov;42(12):2957-63.

PMID:11687542

Abstract

PURPOSE

To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans.

METHODS

The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. Latanoprost (0.005%, 30 microl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NB(ONH) was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NB(ONH) was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NB(ONH) change was also studied in rabbits and monkeys. In humans, the time-course changes in NB(ONH) were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition.

RESULTS

Latanoprost significantly increased NB(ONH) 10% to 19% in treated eyes after a single instillation (P = 0.035) or 7-day instillation regimen (P = 0.035) in rabbits, after a 4-day (P = 0.035) or 7-day (P = 0.035) instillation regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NB(ONH) increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (P > 0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P < 0.05) and humans (P < 0.05).

CONCLUSIONS

Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.

摘要

目的

评估局部应用拉坦前列素对荷兰兔、食蟹猴和正常人视神经乳头（ONH）血液循环的影响。

方法

采用激光散斑法测定ONH组织血流速度（NB(ONH)）。将拉坦前列素（0.005%，30微升）滴入一只眼，另一只眼滴入赋形剂作为对照。在兔中，单次滴入后90分钟以及每日滴入一次、持续7天的给药方案前后测量NB(ONH)。在猴中，每日滴入一次、持续1、4和7天的给药方案前后测量NB(ONH)。还在兔和猴中研究了静脉注射吲哚美辛对拉坦前列素诱导的NB(ONH)变化的影响。在人类中，每日滴入一次、持续7天的给药方案前后4.5小时测量NB(ONH)的时间进程变化。每个实验同时研究眼压（IOP）和全身参数。所有测量均由对实验条件不知情的研究者进行。

结果

在兔中，单次滴入（P = 0.035）或每日滴入一次、持续7天的给药方案后（P = 0.035），拉坦前列素使治疗眼的NB(ONH)显著增加10%至19%；在猴中，每日滴入一次、持续4天（P = 0.035）或7天（P = 0.035）的给药方案后，以及在人类中，每日滴入一次、持续7天的给药方案后（P = 0.013），拉坦前列素使治疗眼的NB(ONH)显著增加，而在任何实验中，赋形剂治疗的眼均无显著变化（P > 0.5）。在兔和猴中，吲哚美辛（5毫克/千克）预处理消除了拉坦前列素治疗眼的NB(ONH)增加，但未消除眼压降低。兔的双眼眼压均无变化（P > 0.4），而猴和人类中仅拉坦前列素治疗眼的眼压显著降低（P < 0.05）。