Wang Rong-Fang, Williamson Jennifer E, Kopczynski Casey, Serle Janet B
*Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY †Aerie Pharmaceuticals Inc., Research Triangle Park, NC.
J Glaucoma. 2015 Jan;24(1):51-4. doi: 10.1097/IJG.0b013e3182952213.
To determine the mechanism by which topically applied AR-13324, a rho kinase inhibitor, and an inhibitor of the norepinephrine transporter, reduces intraocular pressure (IOP) in normotensive monkey eyes.
Seven normotensive monkeys were used. Tonographic outflow facility (C) was measured before drug administration and repeated 6 hours after administration of 50 µL (25 µL×2) of 0.04% AR-13324 to 1 eye and an equal volume of vehicle to the contralateral control eye. Baseline aqueous humor flow rates (F) were measured hourly for 6 hours beginning at 10:00 AM on day 1. On day 2, 50 µL (25 µL×2) of 0.04% AR-13324 was applied to 1 eye of each animal and vehicle to the fellow eye at 8:00 AM. Aqueous humor flow rates were measured at the same times as on the baseline day beginning 2 hours after dosing.
Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, C was increased (P<0.05) by 53% in drug-treated eyes compared with either contralateral vehicle-treated control eyes or baseline measurements. The IOP measured by pneumatonometer in treated eyes was reduced (P<0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes. For 6 hours after a single dose of 0.04% AR-13324, F was reduced (P<0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively.
AR-13324 reduces IOP in normotensive monkey eyes. A dual mechanism of action, increase in tonographic outflow facility, and decrease of aqueous humor flow rates, accounts for the IOP reduction in normotensive monkey eyes.
确定局部应用的AR-13324（一种Rho激酶抑制剂和去甲肾上腺素转运体抑制剂）降低正常血压猴眼眼压（IOP）的机制。
使用7只正常血压的猴子。在给药前测量眼压描记流出率（C），并在向1只眼睛滴注50μL（25μL×2）0.04% AR-13324且向对侧对照眼睛滴注等量赋形剂6小时后重复测量。从第1天上午10:00开始，每小时测量6小时的基线房水流出率（F）。在第2天上午8:00，向每只动物的1只眼睛应用50μL（25μL×2）0.04% AR-13324，向另一只眼睛应用赋形剂。在给药后2小时开始，与基线日相同的时间测量房水流出率。
在7只正常猴眼单次给予0.04% AR-13324 6小时后，与对侧赋形剂处理的对照眼睛或基线测量值相比，药物处理眼睛的C增加了53%（P<0.05）。与基线测量值相比，用眼压计测量的处理眼睛的IOP降低了25%（P<0.005），与对侧赋形剂处理的眼睛相比降低了24%。在单次给予0.04% AR-13324后的6小时内，与对侧赋形剂处理的眼睛和基线值相比，F分别降低了20%和23%（P<0.05）。
AR-13324可降低正常血压猴眼的眼压。眼压描记流出率增加和房水流出率降低的双重作用机制导致了正常血压猴眼眼压的降低。
