Development of a Next Generation Visual Performance Assessment System for Rodents

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.8. Narrative Our proposal is to develop a fully-automated animal visual function testing device based on the optomotor reflex (OMR) behavior. Our new system enables efficient and unbiased assessment of visual functions including visual acuity and contrast sensitivity in rodents. This platform will provide a powerful “turnkey” toolkit to study eye disease models and discover drugs aimed at treating blinding conditions, such as age-related macular degeneration and glaucoma. It can also be extended to study neurodegenerative diseases, such as Alzheimer’s disease and the aging brain.