Hu Yujie, Gabelt B'Ann True, Kaufman Paul L
Department of Ophthalmology and Visual Sciences, University of Wisconsin, 600 Highland Ave, Madison, WI 53792, USA.
Exp Eye Res. 2006 Jun;82(6):1100-8. doi: 10.1016/j.exer.2005.12.004. Epub 2006 Jan 26.
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 (1 day). Thus, the monkey organ-cultured anterior segment system can be used to determine the effects of pharmacological and biological agents on trabecular outflow.
在完整的灵长类动物活体眼中,除非采用复杂的手术性睫状肌离断或同位素积累程序,否则可能难以确定房水流出功能反应是由于对小梁网的直接作用,还是通过对睫状肌张力的间接作用所致。我们建立了一个仿照人类眼前节器官培养系统的猴眼前节器官培养系统,并确定了其特性以及对H - 7的反应,H - 7是一种在体内和其他器官培养系统中均显示可增加小梁网房水流出的药物。使用猴器官培养眼前节系统进行的房水流出功能研究表明:基线值与体内测量值相当;随着时间推移出现洗脱现象;两级恒压灌注技术所得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房水流出功能和眼压时发现存在种属差异;单因素方差分析显示,两种属中年龄对房水流出功能均无影响;眼前节交换灌注后若在1小时内测量,则房水流出功能增加;对H - 7的反应幅度与体内及其他体外系统报道的相当。与体内猴研究(反应开始于6 - 9分钟)以及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的反应开始时间延迟(H - 7交换后一天)。而且反应持续时间(从开始起2 - 3天)比体外人类研究中发现的持续时间(1天)更长。因此,猴器官培养眼前节系统可用于确定药理和生物制剂对小梁网房水流出的影响。