Measurement of Outflow Facility Using iPerfusion.
Measurement of Outflow Facility Using iPerfusion.
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DOI：
10.1371/journal.pone.0150694
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Overby DR
中科院分区：
文献类型：
--
作者：
Sherwood JM;Reina-Torres E;Bertrand JA;Rowe B;Overby DR
眼内压升高是青光眼的主要危险因素，降低眼内压是防止青光眼进一步视力丧失的唯一成功策略。IOP由房水分泌和流出速率之间的平衡决定，并且流出的水力传导性的病理性降低（称为流出功能）是青光眼中IOP升高的原因。小鼠模型通常用于研究控制流出便利性的机制，但小鼠眼睛的微小尺寸使得流出测量在技术上具有挑战性。在这项研究中，我们提出了一种使用iPerfusion™测量和分析流出设施的新方法，该方法集成了一个驱动式压力储存器、热流量传感器、压差测量和一个自动化计算机化界面。在C57 BL/6 J小鼠的眼球摘除中，流量-压力关系是高度非线性的，并且由描述流出设施的压力依赖性的经验幂律模型很好地表示。在零压力下，测得的流量与零不可区分，确认在摘除的眼睛中不存在任何显著的压力无关流量。与常用的两参数线性流出模型的比较表明，不适当的应用程序的线性拟合的非线性流量压力关系引入了相当大的误差，在流出设施的估计，并导致压力无关的流出的假象。来自C57 BL/6 J小鼠的摘除眼的群体的数据显示，流出便利性最好由对数正态分布描述，个体之间具有6倍的变异性，但在同侧眼之间具有相对紧密的便利性相关性。iPerfusion代表了一种平台技术，用于准确和稳健地确定摘除小鼠眼睛中的流量-压力关系，用于青光眼研究，并进行微小修改，可在体内应用于小鼠以及其他物种或不同生物流体系统的眼睛。
Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems.