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

• 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
• 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' 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

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.项目总结 标题：新一代啮齿动物视觉表现评估系统的开发 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疾病有关，特别是与阿尔茨海默病、帕金森氏症有关 疾病和创伤性脑损伤。视运动反射(OMR)由先天的、反射性的头和/或身体-- 在视觉运动反应过程中的运动，一直是测量视觉功能的传统方法。它 正在成为视觉研究领域基因功能表型和药物筛选的有力工具， 因为它为对比敏感度和视力提供了非侵入性和临床相关的评估。 随着神经退行性疾病的临床前开发和治疗策略的评估 依赖于啮齿动物模型，特别是老鼠模型，一种用于评估啮齿动物视觉表现的OMR设备 需求尤其旺盛。然而，现有的OMR系统要么是主观的(手动评分)，要么是有缺陷的 因为他们依赖任意的时间窗口或不匹配的盲目动物作为参考来确定视力极限。 此外，测试程序没有得到优化，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对治疗效果和基因功能行为的评估 视觉科学领域中的表型分析。 在我们完成的第一阶段项目(R41 EY025913)中，我们严格地解决了现有OMR的缺点 系统。我们的努力导致了一种新的OMR系统，该系统利用了正在申请专利的技术。我们的新奇之处 系统在于负的OMR指示器，它是我们独特算法的基础。；此算法启用 研究人员需要区分视力受损和不顺从的动物。我们优化的测试方案 使用阶梯翻转程序，允许快速、无偏见和全自动的视觉评估。 我们的系统原型产生了高效和准确的鼠标视觉实时量化 具有高灵敏度和重复性的性能。 这项SBIR第二期工程的具体目标是(1)开发一个“交钥匙”的OMR系统，(2)验证 系统采用多只视网膜退行性变小鼠模型，并以验证测试协议为指导，方便 它的应用，以及(3)完善杆和锥的特定功能识别系统。一个平台 小鼠和大鼠的视觉行为评估将极大地促进药物发现过程，旨在预防 或减缓视力丧失或恢复视力。从而，我们的产品将有效地加速发展 治疗严重失明情况，包括老年性黄斑变性和青光眼。在 未来，该系统将扩大规模，其应用将扩大到评估老化的大脑和 神经退行性疾病模型，如阿尔茨海默病，通过测量对 各种视觉刺激。