Development of a Next Generation Visual Performance Assessment System for Rodents

7.项目摘要 标题：下一代啮齿动物视觉性能评估系统的开发 视觉行为异常不仅与视网膜病变和视觉通路障碍直接相关， 与许多神经退行性脑部疾病有关，特别是阿尔茨海默病，帕金森病， 疾病和创伤性脑损伤视动反射（optomotor reflex，OMR）由先天的、反射性的头部和/或身体组成。 在视觉运动反应期间的运动，并且已经是用于测量视觉功能的常规方法。它 正在成为视觉研究领域基因功能表型分析和药物筛选的有力工具， 因为它为对比敏感度和视敏度提供了非侵入性和临床相关的评估。 由于神经退行性疾病的临床前开发和治疗策略的评价是高度重要的， 依赖于啮齿动物模型，特别是小鼠模型，用于评估啮齿动物视觉表现的OMR装置 特别需要。然而，现有的OMR系统要么是主观的（手动评分的OMR），要么是有缺陷的 因为它们依赖于任意的时间窗或不匹配的盲动物作为参考来确定视力极限。 此外，测试程序尚未优化，而且很耗时。现有OMR的局限性 技术和设备在很大程度上阻碍了治疗效果和基因功能行为的评估 视觉科学领域的表型分析。 在已完成的第一阶段项目（R41 EY 025913）中，我们认真解决了现有OMR的缺点 系统.我们的努力已经导致了一个新的OMR系统，利用正在申请专利的技术。我们的新奇 系统的关键在于负OMR指标，这是我们独特算法的基础。该算法使 研究人员区分视力受损和不顺从的动物。我们优化的测试方案 使用阶梯反转程序，可进行快速、无偏倚和全自动的视觉评估。 我们的原型系统产生有效和准确的实时量化小鼠视觉 具有高灵敏度和重现性的性能。 SBIR第二阶段项目的具体目标是：（1）开发一个“交钥匙”OMR系统，（2）验证 系统与多个视网膜变性小鼠模型，并验证测试协议作为指导，以促进 其应用，和（3）完善系统的杆和锥特异性功能的歧视。的平台 小鼠和大鼠的视觉行为评估将极大地促进旨在预防的药物发现过程。 或减缓视力丧失或恢复视力。从而，我们的产品将加速有效的开发 治疗包括老年性黄斑变性和青光眼在内的破坏性致盲疾病。在 未来，该系统将按比例扩大，其应用将扩展到评估老化的大脑， 神经退行性疾病模型，如阿尔茨海默病，通过测量行为反应， 各种视觉刺激。

7. PROJECT SUMMARY Title: Development of a Next Generation Visual Performance Assessment System for Rodents Visual behavior abnormalities not only link directly to the retinal pathology and visual pathway disorders, but also associate with many neurodegenerative brain conditions, particularly with Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. The optomotor reflex (OMR) consists of innate, reflexive head and/or body- movements during optomotor responses and has been a conventional method for measuring visual functions. It is emerging as a powerful tool for gene function phenotyping and drug screening in the vision research field, because it offers noninvasive and clinically-relevant assessments for contrast sensitivity and visual acuity. As preclinical development and evaluation of treatment strategies for neurodegenerative diseases are highly dependent on rodent models, especially mouse models, an OMR device for assessing rodent visual performance is in particular demand. However, existing OMR systems are either subjective (manually-scored OMR) or flawed as they rely on an arbitrary time window or an unmatched blind animal as a reference to determine vision limits. Also, the test procedure has not been optimized and is time consuming. The limitations of existing OMR technology and devices have largely hindered the evaluation of treatment efficacy and gene function behavior phenotyping in the field of vision science. In our completed Phase I project (R41 EY025913), we critically addressed the shortcomings of the existing OMR systems. Our effort has led to a new OMR system which utilizes patent-pending technology. The novelty of our system lies in the negative OMR indicator that underlies our unique algorithm. ; this algorithm enables researchers to distinguish between visually-impaired and noncompliant animals. Our optimized testing protocol uses a staircase reversal procedure, which allows for rapid, unbiased, and fully-automated visual assessment. The prototype of our system produces efficient and accurate real-time quantification of mouse visual performance with high sensitivity and reproducibility. The Specific Aims of this SBIR Phase II project are (1) to develop a “turnkey” OMR system, (2) to validate the system with multiple retina degenerative mouse models, and authenticate the test protocol as a guide to facilitate its application, and (3) to refine the system for rod- and cone-specific function discrimination. A platform for mouse and rat visual behavior assessment will greatly facilitate the drug discovery process aimed at preventing or slowing vision loss or restoring sight. Thereby, our product will accelerate the development of effective treatments for devastating blinding conditions including age-related macular degeneration and glaucoma. In the future, the system will be scaled up, and its application will be expanded to evaluate the aging brain and neurodegenerative disease models, such as Alzheimer’s disease, by measuring behavior responses toward various visual stimuli.