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. 项目概要标题：开发下一代啮齿动物视觉表现评估系统视觉行为异常不仅与视网膜病理和视觉通路障碍直接相关，而且还与与许多神经退行性脑部疾病有关，特别是阿尔茨海默病、帕金森病视运动反射 (OMR) 包括先天的、反射性的头部和/或身体反射。视运动反应期间的运动，一直是测量视觉功能的传统方法。正在成为视觉研究领域基因功能表型分析和药物筛选的强大工具，因为它提供了对对比敏感度和视力的无创且临床相关的评估。由于神经退行性疾病治疗策略的临床前开发和评估高度重视依赖于啮齿动物模型，尤其是小鼠模型，用于评估啮齿动物视觉表现的 OMR 设备然而，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。因为他们依靠任意时间窗口或无与伦比的失明动物作为视力确定极限的参考。此外，测试程序尚未优化且耗时。现有 OMR 的局限性。技术和设备在很大程度上阻碍了治疗效果和基因功能行为的评估视觉科学领域的表型分析。在我们已完成的第一阶段项目（R41 EY025913）中，我们批判性地解决了现有 OMR 的缺点我们的努力催生了一种新的 OMR 系统，该系统利用了我们正在申请专利的技术的新颖性。系统在于负 OMR 指标，该指标是我们独特算法的基础；研究人员可以区分视力受损的动物和不合规的动物。使用楼梯反转程序，可以进行快速、公正和全自动的视觉评估。我们的系统原型可对鼠标视觉进行高效、准确的实时量化性能具有高灵敏度和重现性。该 SBIR 第二阶段项目的具体目标是 (1) 开发“交钥匙”OMR 系统，(2) 验证系统与多个视网膜退化小鼠模型，并验证测试协议作为指导，以促进其应用，以及（3）完善视杆细胞和视锥细胞特定功能区分的系统。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性的发展。治疗破坏性致盲疾病，包括年龄相关性黄斑变性和青光眼。未来，该系统将扩大规模，其应用范围将扩大到评估大脑老化和通过测量行为反应来建立神经退行性疾病模型，例如阿尔茨海默病各种视觉刺激。