Nilsson Siv F E, Drecoll Enken, Lütjen-Drecoll Elke, Toris Carol B, Krauss Achim H-P, Kharlamb Alexander, Nieves Amelia, Guerra Teresa, Woodward David F
Department of Medicine and Care, Division of Pharmacology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4042-9. doi: 10.1167/iovs.05-1627.
To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action.
All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies.
Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 +/- 0.20 vs. 0.53 +/- 0.18 microL.min(-1). After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes.
The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.
研究前列腺素EP2受体激动剂布他前列素的降眼压作用并确定其作用机制。
所有实验均在局部应用布他前列素（0.1%）后的食蟹猴身上进行。通过荧光光度法测定布他前列素对房水流出的影响。采用两级恒压灌注法测量总流出率，通过向前房灌注异硫氰酸荧光素标记的葡聚糖来测定葡萄膜巩膜流出。在用布他前列素进行长期治疗的动物中，通过经心脏灌注多聚甲醛和眼球浸泡固定进行组织固定后，研究其对眼部形态的影响。清醒的眼压正常的猴子和单侧高眼压的猴子用于眼压（IOP）研究。
布他前列素对眼压正常的猴子的房水流出或总流出率没有显著影响。布他前列素治疗组眼睛的葡萄膜巩膜流出明显高于载体治疗组眼睛，分别为1.03±0.20与0.53±0.18微升·分钟-1。用布他前列素治疗1年后，睫状肌形态发生改变，表现为睫状肌束之间的间隙增加以及明显形成新的流出通道。在许多情况下，小梁网也观察到了变化。单次0.1%剂量的布他前列素可使眼压正常的猴子眼压显著降低，并使激光诱导性青光眼猴子眼睛的眼压降低至与对侧眼压正常眼睛相同的水平。
根据生理和形态学研究结果，前列腺素EP2受体激动剂布他前列素似乎通过增加葡萄膜巩膜流出而降低眼压。尽管前列腺素EP2受体在结构和功能上与FP受体不同，但EP2和FP受体刺激对房水流出的影响相似。
