Husain Shahid, Whitlock N Andy, Rice Dennis S, Crosson Craig E
Hewitt Laboratory of the Ola B Williams Glaucoma Center, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
Exp Eye Res. 2006 Dec;83(6):1453-8. doi: 10.1016/j.exer.2006.08.004. Epub 2006 Oct 6.
The aim of the present study was to evaluate the effects of the prostaglandin F2 alpha analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1+/-0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2+/-0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED50 values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This prolonged hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins.
本研究的目的是评估前列腺素F2α类似物拉坦前列素对啮齿动物眼内压（IOP）的影响。啮齿动物在青光眼研究中的应用越来越广泛；然而，关于前列腺素对啮齿动物眼内压作用的结果却相互矛盾。在Wistar大鼠中，单剂量的拉坦前列素（60 ng）可使眼内压产生双相变化：最初眼压升高（2.1±0.7 mmHg），在2小时时达到峰值，随后出现长时间的低血压，眼压在5小时时降至最低（5.2±0.7 mmHg）。拉坦前列素的升压和降压作用均与剂量相关，其ED50值分别为108和5.2 ng。这些反应可被4%毛果芸香碱预处理所拮抗。在棕色挪威大鼠和C57BL/6小鼠中，单剂量的拉坦前列素也可使眼内压产生双相反应，最初眼压升高，在1至2小时之间达到峰值，随后在4至8小时内出现长时间的低血压。这些结果表明，在啮齿动物中，局部应用拉坦前列素引起的眼内压反应的特征是先出现高血压，随后是长时间的低血压。这种长时间的低血压与在猴子和人类中测得的情况相似。综上所述，这些结果支持了啮齿动物可作为体内模型来研究眼降压药物（如前列腺素）作用的观点。
