依他尼酸对人眼小梁网内壁及房水流出功能的影响。

Effects of ethacrynic acid on Schlemm's canal inner wall and outflow facility in human eyes.

作者信息

Ethier C R, Coloma F M

机构信息

Department of Mechanical and Industrial Engineering, University of Toronto, Ontario, Canada.

出版信息

Invest Ophthalmol Vis Sci. 1999 Jun;40(7):1599-607.

PMID:10359344

Abstract

PURPOSE

The role of the inner wall of Schlemm's canal in determining aqueous outflow facility is poorly understood. To quantify the relationship between inner wall pore characteristics and aqueous outflow facility in human eyes, both control eyes and eyes in which facility had been pharmacologically increased by ethacrynic acid (ECA) infusion were studied.

METHODS

Outflow facility was measured in enucleated human eyes before and after delivery of 0.25 mM ECA (one eye of each of 6 pairs) or 2.5 mM ECA (one eye of each of 13 pairs). ECA, and vehicle in contralateral eyes, was delivered into Schlemm's canal by retroperfusion, thereby largely avoiding drug exposure to the trabecular meshwork. After facility measurement, eyes were fixed under conditions of either constant pressure (physiological intraocular pressure, 13 pairs) or "equal flow" (6 pairs) and were microdissected to expose the inner wall of Schlemm's canal. The density and diameter of intercellular and intracellular inner wall pores were measured using scanning electron microscopy.

RESULTS

Retroperfusion with 2.5 mM ECA increased facility by 73% (P < 0.001), whereas 0.25 mM ECA increased facility by 19% (not statistically significant). The density of intercellular pores in the inner wall of Schlemm's canal was increased by 520% in 2.5 mM ECA-retroperfused eyes (P < 0.00004), whereas intracellular pore density remained approximately constant. Large pores (size > or = 1.1 microm) were particularly enhanced in ECA retroperfused eyes. The net change in facility due to ECA was not correlated with changes in pore density or other inner wall pore statistics.

CONCLUSIONS

Our data are most consistent with a model in which pores in the inner wall of Schlemm's canal indirectly influence facility. However, measured changes in facility due to changes in inner wall properties did not agree with quantitative predictions of the pore funneling theory, suggesting that changes in facility may instead be due to gel leakage from the extracellular spaces of the juxtacanalicular tissue. More definitive experiments are required to confirm this hypothesis.

摘要

目的

施莱姆管内壁在决定房水流出易度方面的作用尚不清楚。为了量化人眼内壁孔隙特征与房水流出易度之间的关系，对对照眼以及通过静脉滴注依他尼酸（ECA）使流出易度药理学增加的眼睛进行了研究。

方法

在6对眼睛中的每对各一只眼睛中滴注0.25 mM ECA，在13对眼睛中的每对各一只眼睛中滴注2.5 mM ECA，然后在摘除的人眼中测量给药前后的流出易度。通过逆向灌注将ECA以及对侧眼的赋形剂注入施莱姆管，从而在很大程度上避免药物暴露于小梁网。在测量流出易度后，将眼睛在恒压（生理眼压，13对）或“等流量”（6对）条件下固定，并进行显微解剖以暴露施莱姆管的内壁。使用扫描电子显微镜测量细胞间和细胞内内壁孔隙的密度和直径。

结果

用2.5 mM ECA逆向灌注使流出易度增加了73%（P < 0.001），而0.25 mM ECA使流出易度增加了19%（无统计学意义）。在2.5 mM ECA逆向灌注的眼睛中，施莱姆管内壁的细胞间孔隙密度增加了520%（P < 0.00004），而细胞内孔隙密度基本保持不变。在ECA逆向灌注的眼睛中，大孔隙（尺寸≥1.1微米）尤其增多。ECA导致的流出易度净变化与孔隙密度或其他内壁孔隙统计数据的变化无关。