Non-invasive assessment of murine intraocular pressure

描述：(申请者摘要)动物模型中的遗传学研究依赖于 主要是在老鼠身上。对青光眼的研究需要测量眼内 压力(IOP)，这对小鼠来说是非常困难的。NEI R03的目标是 建议开发一种标准化的、非侵入性的眼压测量方法 老鼠。为了实现这一目标，我们将修改、测试和验证 感应冲击(1/1)眼压测量法。一种基于此的眼压计 方法简单，可以用相对便宜的组件制造，并且 应为延长时间的重复测量提供可靠的数据 句号。它将允许重复测量眼压，而不会影响 眼睛生理学。改进专门用于小鼠眼压的1/1方法 为了测量，我们将进行操纵以下变量的实验： 探头的质量和设计、探头的磁化强度、线圈特性和 探测速度。我们还将优化使用探测器的软件算法 确定眼压的运动参数。量表的效度、准确性和可靠性 眼压测量将与测压眼压测定进行对比测试。下一步，到 演示实用程序，它将用于每隔2个月监测一次眼压 到i岁，在几个品系的近交系小鼠中，通常用于遗传 实验。I/I方法跟踪年龄相关增长的能力 自发性青光眼闭角型青光眼的眼压 将对DBA/2小鼠的亚系进行测试。最后，因为青光眼是一种 影响视网膜神经节细胞及其轴突的疾病，我们将评估 三种方法测得的眼压与眼压的相关性 DBA/2小鼠RGC数量和分布模式的变化 这是我们实验室以前开发的一种准确的方法 对无抽样偏差的大鼠视网膜神经节细胞进行量化。 这一试点项目的成功完成将为进一步 以小鼠为模型研究青光眼发病机制 将提供高吞吐量的方法，可用于遗传和其他 学习。

DESCRIPTION: (Applicant's Abstract) Genetic studies in animal models rely primarily on mice. Studies on glaucoma require measurement of intraocular pressure (IOP) which is very difficult in mice. The goal of this NEI R03 proposal is to develop a standardized, non-invasive method for measuring IOP in mice. To achieve this goal, we will modify, test and validate an induction-driven impact (1/1) tonometry method. A tonometer based on this method is simple, can be made with relatively inexpensive components, and should provide reliable data for repeated measurements over extended time periods. It will allow for repetitive measurement of IOP without affecting ocular physiology. To refine the 1/1 method specifically for use in mouse IOP measurement, we will conduct experiments manipulating the following variables: mass and design of the probe, probe magnetization, coil characteristics and probe speed. We will also optimize the software algorithm that uses probe movement parameters to determine IOP. The validity, accuracy and reliability of IOP measurement will be tested against manometric IOP determinations. Next, to demonstrate utility, it will be used to monitor IOP at 2-monthly intervals up to I year of age, in several strains of inbred mice commonly used for genetic experiments. The ability of the I/I method to track the age-dependent increase in IOP in the closed-angle type of glaucoma that develops spontaneously in two substrains of the DBA/2 mouse will be tested. Finally, because glaucoma is a disease affecting retinal ganglion cells and their axons, we will assess the correlation between IOP measurements obtained with the III method and the changes in number and pattern of RGC distribution in DBA/2 mice, adapting a method that has been previously developed in our laboratory for accurately quantifying ganglion cells in the rat retina that has no sampling bias. Successful completion of this pilot project will create a platform for further research in understanding the pathogenesis of glaucoma using mice as models and will provide high throughput methods that can be used for genetic and other studies.