Gabelt B'Ann T, Seeman Jennifer L, Podos Steven M, Mittag Thom W, Kaufman Paul L
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792, USA.
Invest Ophthalmol Vis Sci. 2004 Mar;45(3):892-9. doi: 10.1167/iovs.03-0911.
To determine in normotensive cynomolgus monkeys, the effects of topical 8-iso prostaglandin (PG)E(2) on intraocular pressure (IOP), aqueous humor formation (AHF), uveoscleral outflow (Fu), and total and trabecular outflow facility.
IOP was measured by Goldmann applanation tonometry under ketamine anesthesia after single or twice-daily topical treatments with 8-iso PGE(2). With animals under pentobarbital anesthesia, AHF and flow to blood (equated to trabecular outflow) were determined by anterior chamber perfusion with radioactively labeled albumin solution. Fu and trabecular outflow facility were calculated from these measurements. Total outflow facility was measured by two-level, constant-pressure perfusion.
IOP was not significantly changed after single or multiple 10- micro g doses of 8-iso PGE(2). The 25- micro g dose significantly decreased IOP by 2 to 3 mm Hg compared to the contralateral vehicle-treated control 4 to 6 hours after a single dose and by 3 to 5 mm Hg within 1.5 hours after twice-daily treatments for 4 to 5 days. Total outflow facility corrected for control eye washout was increased by an apparent 37% (P < 0.02, n = 7) from 2 to 3.5 hours after the ninth dose, largely due to outlier values obtained in one monkey. Isotope studies performed after twice-daily treatments totaling 9 to 29 doses showed no change in AHF, trabecular outflow facility, or total outflow facility. Relative to AHF, trabecular outflow was significantly decreased, and the calculated Fu was significantly increased when all data were analyzed.
The present findings are consistent with lowering of IOP by 8-iso PGE(2), primarily by increasing Fu. A direct effect on the trabecular meshwork was not indicated by these in vivo studies.
在血压正常的食蟹猴中，确定局部应用8-异前列腺素（PG）E2对眼压（IOP）、房水生成（AHF）、葡萄膜巩膜流出（Fu）以及总流出和小梁流出系数的影响。
在氯胺酮麻醉下，通过Goldmann压平眼压计测量单次或每日两次局部应用8-异前列腺素E2后的眼压。在戊巴比妥麻醉下的动物中，通过用放射性标记的白蛋白溶液进行前房灌注来测定房水生成和流向血液的流量（等同于小梁流出）。根据这些测量结果计算Fu和小梁流出系数。通过两级恒压灌注测量总流出系数。
单次或多次给予10μg剂量的8-异前列腺素E2后，眼压无显著变化。单次给药后4至6小时，25μg剂量与对侧用赋形剂处理的对照相比，眼压显著降低2至3mmHg，每日两次给药4至5天后，在1.5小时内眼压降低3至5mmHg。在第九次给药后2至3.5小时，校正对照眼冲洗后的总流出系数明显增加了37%（P<0.02，n = 7），这主要是由于一只猴子获得的异常值。在总共进行9至29次每日两次给药后进行的同位素研究表明，房水生成、小梁流出系数或总流出系数没有变化。当分析所有数据时，相对于房水生成，小梁流出显著减少，计算得出的Fu显著增加。
目前的研究结果与8-异前列腺素E2降低眼压一致，主要是通过增加Fu。这些体内研究未表明对小梁网有直接作用。
