TAS::75 0862::TAS R&D-OTHER R & D-B RES

需要能够在中等到高度进行的高度预测性的毒理学检测 这样就减少了对哺乳动物模型的依赖。而生化和基于细胞的分析 提供高吞吐量它们不会对广泛的开发和 整个动物试验所能提供的生理效应。以斑马鱼为基础的毒理学检测可能 代表了一种中间立场，允许大大减少对哺乳动物和其他成年脊椎动物的依赖 模型生物体，同时保留了这些系统的许多优点。 整个技术目标是开发一种基于多普勒-OCT的自动成像系统，用于 使用斑马鱼模型进行毒理学研究。这些检测将通过以下方式识别发育和心脏毒素 测量形态特征，如长度、曲率和其他偏离 正常的斑马鱼胚胎比例，以及心率，节律， 和心输出量。我们预计在第一阶段计划期间产生的初步数据将 论证斑马鱼作为毒理学模型的可行性，并将展示 成像系统测量与毒性相关的关键参数。

There is a need for highly predictive toxicological assays that can be performed at moderate to high throughput and that reduce reliance on mammalian models. While biochemical and cell-based assays provide high-throughput they do not provide the sensitivity to the broad range of developmental and physiological effects that whole animal testing can provide. Zebrafish-based toxicology assays may represent a middle ground that permits greatly reduced reliance on mammals and other adult vertebrate model organisms while retaining many advantages of those systems. The overall technical objective is to develop an automated Doppler-OCT based imaging system for toxicological studies using zebrafish models. Those assays will identify developmental and cardiac toxins by measuring morphological characteristics such as length, degree of curvature and other deviations from normal zebrafish embryonic proportions, as well as physiological characteristics such as heart rate, rhythm, and cardiac output. We anticipate that preliminary data generated during the Phase I program will demonstrate the feasibility of the zebrafish as a toxicological model and will demonstrate the ability of the imaging system to measure key parameters correlated with toxicity.