Non-invasive assessment of murine intraocular pressure

描述：（申请人的摘要）动物模型中的遗传研究依赖于 主要是老鼠。青光眼的研究需要测量眼内 眼压（IOP），这在小鼠中是非常困难的。本次NEI R 03的目标 建议开发一种标准化的，非侵入性的方法来测量IOP， 小鼠为了实现这一目标，我们将修改、测试和验证 感应驱动冲击（1/1）眼压测量法。基于此的眼压计 方法简单，可以用相对便宜的组件制成， 应该为长时间重复测量提供可靠的数据 时期它将允许重复测量IOP，而不会影响 眼生理学改进专门用于小鼠IOP的1/1方法 测量，我们将进行实验操作以下变量： 探头的质量和设计、探头磁化、线圈特性和 探头速度我们还将优化使用探针的软件算法 运动参数以确定IOP。的效度、准确性和信度 将根据眼压计IOP测定值对IOP测量值进行测试。接下来， 证明实用性，它将用于监测IOP，每隔2个月一次， 到1岁，在几个品系的近交系小鼠通常用于遗传 实验I/I方法跟踪年龄依赖性增加的能力 闭角型青光眼的IOP， 将测试DBA/2小鼠的亚系。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 用III方法获得的IOP测量值与 DBA/2小鼠RGC数量和分布模式的变化，适应了一种新的免疫调节机制。 我们实验室以前开发的方法， 量化大鼠视网膜中的神经节细胞，没有采样偏差。 这一试点项目的成功完成将为进一步开展 以小鼠为模型的青光眼发病机制研究， 将提供可用于遗传和其他目的的高通量方法， 问题研究

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.