Development of a Next Generation Visual Performance Assessment System for Rodents

开发下一代啮齿动物视觉表现评估系统

基本信息

批准号：
9920144
负责人：
Dong Feng Chen
金额：
$ 69.17万
依托单位：
AFASCI, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9920144
关键词：
Address Age related macular degeneration Algorithms Alzheimer&apos s Disease Animal Testing Animals Automation Behavior Behavior assessment Behavior monitoring Blindness Brain Brain Diseases Canada Cerebrum Comparative Study Computational algorithm Computer software Cone Consumption Contrast Sensitivity Development Devices Discrimination Disease model Drug Screening Engineering Evaluation Eye Eye Movements Eye diseases Future Gene Mutation Generations Germany Glaucoma Goals Grant Head Head Movements Histology Inherited Laboratories Legal patent Light Link Manuals Measurement Measures Mechanics Mediating Medical Methods Movement Mus Nerve Degeneration Neurodegenerative Disorders Optical Coherence Tomography Parkinson Disease Pathology Pharmaceutical Preparations Phase Phenotype Physiology Point Mutation Positioning Attribute Procedures Process Protocols documentation Rattus Reflex action Reproducibility Research Institute Research Personnel Resolution Retina Retinal Degeneration Retinitis Pigmentosa Rod Rodent Rodent Model Running Small Business Innovation Research Grant Stimulus System Tablets Technology Testing Time Transducin Translating Translations Traumatic Brain Injury Treatment Efficacy Validation Vertebrate Photoreceptors Vision Vision research Visual Visual Acuity Visual Pathway Disorder Visual impairment Wild Type Mouse aging brain base behavioral phenotyping behavioral response blind clinically relevant commercialization density design drug development drug discovery drug market effective therapy gaze gene function innovation luminance medical schools mouse model next generation non-compliance open source preclinical development preclinical evaluation prevent prototype response rho scale up tool treatment strategy validation studies vision science visual performance visual stimulus

项目摘要

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.

7。项目摘要标题：啮齿动物的下一代视觉性能评估系统的开发视觉行为异常不仅直接链接到视网膜病理和视觉途径疾病，还可以与许多神经退行性的大脑状况相关，特别是与阿尔茨海默氏病，帕金森氏病疾病和创伤性脑损伤。验光反射（OMR）由先天，反身头和/或身体组成验光响应期间的运动是测量视觉功能的常规方法。它正在成为视觉研究领域中基因功能表型和药物筛查的强大工具，因为它为对比度灵敏度和视力提供了无创和临床上的评估。由于神经退行性疾病的临床前发展和评估是高度依赖啮齿动物模型，尤其是鼠标模型，一种用于评估啮齿动物视觉性能的OMR设备特别是需求。但是，现有的OMR系统是主观的（手动评分OMR）或有缺陷当他们依靠任意时间窗口或无与伦比的盲动物作为确定视觉限制的参考。同样，测试程序尚未得到优化，并且耗时。现有OMR的局限性技术和设备在很大程度上阻碍了治疗效率和基因功能行为的评估视觉科学领域的表型。在我们完成的I阶段项目（R41 EY025913）中，我们严格解决了现有OMR的缺点系统。我们的努力导致了一个新的OMR系统，该系统利用了正在申请专利技术的技术。我们的新奇系统在于基础我们独特算法的负OMR指标。 ;该算法可以启用研究人员区分视觉障碍和不合格动物。我们优化的测试协议使用楼梯相反的过程，该过程允许快速，公正和完全自动化的视觉评估。我们系统的原型可产生小鼠视觉的有效，准确的实时定量具有高灵敏度和可重复性的性能。该SBIR II期项目的具体目的是（1）开发“交钥匙” OMR系统，（2）以验证具有多个视网膜退化鼠标模型的系统，并验证测试方案作为促进的指南它的应用和（3）用于完善杆和锥体特异性函数歧视的系统。一个平台鼠标和大鼠视觉行为评估将极大地促进旨在防止的药物发现过程或视力丧失或恢复视力放缓。因此，我们的产品将加速有效的发展毁灭性盲目条件的治疗方法，包括与年龄相关的黄斑变性和青光眼。在未来，该系统将被扩展，并将扩展其应用以评估衰老的大脑和神经退行性疾病模型，例如阿尔茨海默氏病，通过衡量行为反应各种视觉刺激。