局部应用血管紧张素AT1受体拮抗剂CS-088对兔眼压及房水动力学的影响。

The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits.

作者信息

Inoue T, Yokoyoma T, Mori Y, Sasaki Y, Hosokawa T, Yanagisawa H, Koike H

机构信息

Research Laboratories of Neuroscience and Immunology, Sankyo Company Limited, Tokyo, Japan.

出版信息

Curr Eye Res. 2001 Aug;23(2):133-8. doi: 10.1076/ceyr.23.2.133.5473.

DOI:10.1076/ceyr.23.2.133.5473

PMID:11840352

Abstract

PURPOSE

To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics.

METHODS

The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF).

RESULTS

CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed.

CONCLUSIONS

Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.

摘要

目的

评估局部应用血管紧张素AT1受体拮抗剂CS - 088的降眼压效果及其对房水动力学的影响。

方法

在两种兔高眼压模型中研究CS - 088对眼压（IOP）的影响。通过向前房注射α - 糜蛋白酶在白化兔中诱导实验性高眼压（α - 糜蛋白酶兔）。检测单次应用CS - 088的效果。此外，在遗传性高眼压兔（牛眼兔，JWHR bu/bu）中连续3周重复给予CS - 088，并在整个实验过程中监测眼压。还在正常兔中研究CS - 088对房水动力学的影响。在本研究中，分别采用眼压恢复率、二级恒压灌注和荧光素 - 葡聚糖灌注方法来测定房水流入、流出易度和葡萄膜巩膜流出（USF）。

结果

1%和2%的CS - 088可显著降低α - 糜蛋白酶兔的眼压，最大眼压降幅为10.1 mmHg。2% CS - 088获得的最大效果不大于1% CS - 088。在牛眼兔中，2% CS - 088也显著降低了眼压。噻吗洛尔在两种模型中均有效。在房水动力学研究中，局部应用CS - 088后可见USF略有增加（17%），而未观察到房水流入或流出易度的变化。