Prostaglandins increase trabecular meshwork outflow facility in cultured human anterior segments
Prostaglandins increase trabecular meshwork outflow facility in cultured human anterior segments
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DOI：
10.1016/j.ajo.2007.09.001
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Johnson, Douglas H.
中科院分区：
文献类型：
--
作者：
Bahler, Cindy K.;Howell, Kyle G.;Johnson, Douglas H.
目的：观察拉坦前列素游离酸和前列腺素E1（PGE 1）对培养的人眼前节流出道功能的影响。临床研究发现前列腺素治疗增加了葡萄膜巩膜流出量，但对小梁流出量是否增加存在分歧。培养的眼前段消除葡萄膜巩膜途径，使直接评估小梁outflow.DESIGN：Laboratory investigation.METHODS：一个眼前段的一对眼睛被放置在灌注器官培养，并接受了连续输注的药物，而其他眼前段收到车辆。评估组织学变化。采用酶谱法和蛋白质印迹法分析基质金属蛋白酶（MMP）活性。结果：拉坦前列素显著增加了流出功能（67% +/- 11% vs对照组6% +/-10%，P <0.001）。设施变化发生在接受药物后1小时内，24小时达到新的基线。设施变化是可逆的，需要约48小时才能恢复到给药前的值。PGE 1引起的设施改变较少（13% +/- 17% vs对照组1% +/-11%，P =.02）。前列腺素治疗的前段有局灶性脱离和Schlemm管内皮细胞丢失的区域，一些区域下面有细胞外基质丢失。MMPs在蛋白质印迹、酶谱或免疫组织化学中并没有持续增加。巩膜水力传导率增加，但不足以占总facilityincreasing.CONCLUSIONS：前列腺素增加流出设施在灌注器官培养人眼前段。MMP活性没有持续增加，巩膜导水率没有增加到足以解释总设施的增加。组织学改变提示直接小梁网效应。
PURPOSE: To determine the effect of latanoprost free acid and prostaglandin E1 (PGE1) on outflow facility in cultured human anterior segments. Clinical studies find prostaglandin treatment increases uveoscleral outflow, but do not agree whether trabecular outflow increases. Cultured anterior segments eliminate the uveoscleral pathway and enable a direct assessment of trabecular outflow.DESIGN: Laboratory investigation.METHODS: One anterior segment of an eye pair was placed in perfusion organ culture and received a continuous infusion of drug while the fellow anterior segment received vehicle. Histologic changes were assessed. Zymography and Western blots were used to analyze matrix metalloprotease (MMP) activity. Scleral hydraulic conductivities were measured.RESULTS: Latanoprost significantly increased outflow facility (67% +/- 11% vs control 6% +/- 10%, P < .001). Facility changes occurred within one hour of receiving drug, reaching a new baseline by 24 hours. Facility changes were reversible, requiring about 48 hours to return to pre-drug values. PGE1 caused less facility change (13% +/- 17% vs control 1% +/- 11%, P =.02). Prostaglandin treated anterior segments had regions of focal detachment and loss of Schlemm canal endothelial Cells, with loss of extracellular matrix underlying some areas. MMPs were not consistently increased in Western blots, zymography, or immunohistochemistry. Scleral hydraulic conductivity increased, but not enough to account for total facility increase.CONCLUSIONS: Prostaglandins increase outflow facility in perfusion organ culture of human anterior segments. MMP activity was not consistently increased, and scleral hydraulic conductivity was not increased sufficiently to account for total facility increase. The histologic changes suggest a direct trabecular meshwork effect.