Wang R F, Lee P Y, Mittag T W, Podos S M, Serle J B, Becker B
Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Arch Ophthalmol. 1998 Sep;116(9):1213-6. doi: 10.1001/archopht.116.9.1213.
To evaluate the effects of 8-iso prostaglandin E2 (8-iso PGE2; prosta-5,13-dien-1-oic acid,11,15-dihydroxy-9-oxo-,[5Z,8beta-11X,13E,15 S]-) on the intraocular pressure (IOP), outflow facility, and aqueous humor flow rates in normal monkeys and monkeys with glaucoma.
The IOP was measured before and as long as 6 hours after the topical application of 8-iso PGE2 to 1 eye of 6 normal monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. The pupil diameter was measured at the same times as the IOP measurements in the normal monkeys. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 6 normal monkeys before and after drug treatment.
In normal monkeys, a single dose of 0.1% 8-iso PGE2 reduced (P<.01) the IOP for 4 hours in the treated eyes with a maximum (mean +/- SEM) reduction of 3.2 +/- 0.2 mm Hg, compared with the contralateral control eyes. The pupil size was smaller (P<.01) in the treated eyes by as much as 1.0 +/- 0.2 mm for 4 hours. In 8 glaucomatous monkey eyes, the application of 0.05% and 0.1% 8-iso PGE2 reduced the IOP (P<.01) for as long as 2 and 5 hours, respectively. The maximum reduction in the IOP was 4.6 +/- 0.8 mm Hg (0.05%) and 6.0 +/- 0.8 mm Hg (0.1%) compared with baseline measurements. The magnitude and duration of the ocular hypotensive effect were enhanced with twice-a-day administration for 5 consecutive days. Outflow facility in normal monkey eyes was increased (P<.05) by 48% in the treated eyes, and aqueous humor flow was unchanged (P>.10), compared with vehicle-treated contralateral control eyes. Mild eyelid edema, conjunctival edema, hyperemia, and discharge appeared in some eyes treated with the 0.1% drug concentration.
The use of 8-iso PGE2 reduces the IOP in both normal and glaucomatous monkey eyes. An increase in outflow facility appears to account for most of the IOP reduction in normal monkeys.
The application of 8-iso PGE2 may have potential for the treatment of glaucoma as an outflow facility-increasing drug.
评估8-异前列腺素E2（8-iso PGE2；前列腺素-5,13-二烯-1-酸，11,15-二羟基-9-氧代-，[5Z,8β-11X,13E,15S]-）对正常猴和青光眼猴眼压（IOP）、房水流出易度及房水流量的影响。
对6只正常猴的1只眼及8只单侧激光诱导性青光眼猴的青光眼眼局部应用8-iso PGE2，在用药前及用药后长达6小时测量眼压。在正常猴测量眼压的同时测量瞳孔直径。对6只正常猴在药物治疗前后测量眼压描记法房水流出易度及荧光光度法房水流量。
在正常猴中，单剂量0.1% 8-iso PGE2使治疗眼的眼压降低（P<0.01）达4小时，最大降低幅度（均值±标准误）为3.2±0.2 mmHg，而对侧对照眼无此变化。治疗眼的瞳孔大小在4小时内缩小（P<0.01）达1.0±0.2 mm。在8只青光眼猴眼中，应用0.05%和0.1% 8-iso PGE2分别使眼压降低（P<0.01）达2小时和5小时。与基线测量值相比，眼压最大降低幅度分别为4.6±0.8 mmHg（0.05%）和6.0±0.8 mmHg（0.1%）。连续5天每日给药2次可增强降眼压作用的幅度和持续时间。与用赋形剂处理的对侧对照眼相比，正常猴治疗眼的房水流出易度增加（P<0.05）48%，房水流量无变化（P>0.10）。在一些用0.1%药物浓度治疗的眼中出现轻度眼睑水肿、结膜水肿、充血和分泌物增多。
8-iso PGE2的应用可降低正常猴和青光眼猴的眼压。在正常猴中，房水流出易度增加似乎是眼压降低的主要原因。
8-iso PGE2作为一种增加房水流出易度的药物，可能具有治疗青光眼的潜力。
