Monkey organ-cultured anterior segments: Technique and response to H-7

Monkey organ-cultured anterior segments: Technique and response to H-7
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DOI:
10.1016/j.exer.2005.12.004
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发表时间:
2006-06-01
影响因子:
3.4
通讯作者:
Kaufman, Paul L.
Kaufman, Paul L.
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Yujie;Gabelt, B'Ann True;Kaufman, Paul L.

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在体内完整的灵长类动物眼睛中,可能很难确定流出设施反应是由于对小梁网的直接影响还是通过对睫状肌张力的影响间接影响,除非使用复杂的手术睫状肌拔除或同位素积累程序。我们以人类眼前段器官培养系统为模型建立了猴子眼前段器官培养系统,并确定了其特征和对 H-7 的反应,H-7 是一种在体内和其他器官培养系统中可增加小梁流出的药物。使用猴子器官培养的眼前节系统进行的流出设施研究表明: 基线值与体内测量值相当;随着时间的推移发生冲刷;两级恒压灌注技术的结果与恒速技术相当;比较恒河猴和食蟹猴器官培养眼前节的基线流出设施和眼压,发现物种差异;通过单向方差分析,年龄对任一物种的流出设施均没有影响;如果在交换后 1 小时内测量,眼前段交换灌注增加流出设施;对 H-7 的反应程度与体内和其他体外系统中报道的反应程度相当。与体内猴研究(起效 6-9 分钟)和体外人类和猪器官培养系统(1 小时内)相比,大多数情况下对 H-7 的反应发生延迟(H-7 交换后第二天)。而且反应持续时间(从开始起 2-3 天)比体外人体研究(1 天)更长。因此,猴子器官培养的眼前段系统可用于确定药理和生物制剂对小梁流出的影响。 (c) 2006 Elsevier Ltd. 保留所有权利。
In the intact primate eye in vivo, it may be difficult to determine whether an outflow facility response is due to direct effects on the trabecular meshwork or indirectly via an effect on ciliary muscle tone unless complicated surgical ciliary muscle disinsertion or isotope accumulation procedures are used. We established a monkey anterior segment organ culture system modeled after the human anterior segment organ culture system and determined its characteristics and response to H-7, an agent shown to increase trabecular outflow in vivo and in other organ culture systems. Outflow facility studies conducted using the monkey organ-cultured anterior segment system showed that: baseline values were comparable to those measured in vivo; washout occurred with time; the two-level constant pressure perfusion technique gave results comparable to the constant rate technique; species differences were found comparing baseline outflow facility and intraocular pressure in rhesus and cynomolgus monkey organ-cultured anterior segments; there was no effect of age on outflow facility in either species by one-way ANOVA; anterior segment exchange perfusion increased outflow facility if measured within 1 hr of the exchange; the magnitude of the response to H-7 was comparable to those reported in vivo and in other in vitro systems. The onset of the response to H-7 was delayed in most cases (day after H-7 exchange), compared to in vivo monkey studies (onset 6-9 min) and in vitro human and porcine organ culture systems (within 1 hr). Also the duration of the response (2-3 days from the onset) was longer than that found for in vitro human studies (I day). Thus, the monkey organ-cultured anterior segment system can be used to determine the effects of pharmacological and biological agents on trabecular outflow. (c) 2006 Elsevier Ltd. All rights reserved.