拉坦前列素和毛果芸香碱对DBA/2J小鼠房水动力学及眼压控制作用的研究

Aqueous humour dynamics of DBA/2J mice and the intraocular pressure response to latanoprost and pilocarpine

目的研究DBA/2J小鼠房水动力学特点及对常用青光眼降眼压药物的反应。方法将实验小鼠按不同月龄(3月龄或10月龄)、不同品系(DBA/2J或C57BL/6)、不同给药药物(0.005%拉坦前列素或0.5%毛果芸香碱),分为8个实验组,8只/组,共128眼。将药物滴于右眼,给药2周;左眼作为自身对照,眼表给予磷酸盐缓冲液。毛果芸香碱每天眼表给药2次(分别在上午9时和下午5时),拉坦前列素每天眼表给药1次(上午9时)。小鼠眼压由Tonolab测量,房水流畅系数采用眼球灌注法测得。结果对于3月龄小鼠,拉坦前列素和毛果芸香碱在C57BL/6和DBA/2J小鼠上降眼压效果良好(眼压下降幅度为13.8%38.9%)。然而,对于10月龄DBA/2J小鼠,毛果芸香碱给药后小鼠眼压与对照眼相比差异无统计学意义(n=8,P>0.05);拉坦前列素的降眼压效果较3月龄DBA/2J小鼠亦有明显下降(5.4mmHgvs.2.6mmHg)。在3月龄和10月龄C57BL/6小鼠上,2种药物的降眼压幅度更为相似。结论DBA/2J小鼠作为青光眼模型,由于其虹膜色素脱离引起小梁网阻塞等特点,并非适合所有降眼压药物的筛选,特别是通过经典通路降眼压的药物。

Objective To study the aqueous humour dynamics of DBA/2J mice and the intraocular pressure response to latanoprost and pilocarpine. Methods The experiment was divided into 8 experimental groups. There were 8 treatment eyes and 8 control eyes in each group, a total of 64 eyes.At the age of 3 months and 10 months, DBA/2J and C57BL/6 mice were topically treated with latanoprost or pilocarpine. Pilocarpine was given twice a day (at 9 a.m. and 5 p.m., respectively), and latanprost once a day (at 9 a.m.). The drugs were applied to the right eye for 2 weeks, and phosphate buffered saline was applied to the left eye which served as a control. The intraocular pressure (IOP) was measured with Tonolab. Mouse eyes were perfused according to an established method. Results At the age of 3 months, drugs significantly decreased IOP in both groups (percentage reduction from 13.8% to 38.9%). However, for 10 months DBA/2J mice,there was no significant difference in IOP in eyes treated with pilocarpine and contralateral controls (n= 8, P>0.05). Similarly,in DBA/2J mice, the magnitude of IOP reduction by latanoprost was lower in 10 months compared with 3 months mice (5.4 mmHg vs. 2.6 mmHg). For 3 months mice, the reduction of IOP in both groups was similar between the two drugs. Conclusions As a glaucoma model, DBA/2J mice are not suitable for the screening of all glaucoma drugs for its characteristics,that trabecular meshwork was blocked by falling iris pigments,especially drugs that decrease IOP only by the classical pathway.