Preclinical evaluation of treatment strategies for retinal neurodegenerative diseases is highly dependent on mouse models. Classical methods to assess the visual function of animals, such as electroretinogram (ERG), which measures electrical responses in the retina, do not address connections between the eye and brain or visual perception by the visual system. This often raises concerns regarding the functional relevance of the therapeutic benefit. Difficulty in assessing visual perception and related behavior in mice and rats, largely due to their subtle visual behavior cues and the lack of adequate measuring devices, presents a critical barrier to the application of mouse models for evaluating treatment efficacy of new drugs, and for scaling up for behavior phenotyping to screen genetic vision defects. Pupillary light reflex (PLR) and optokinetic reflex (OKR) tests are useful methods in clinics for assessing human visual responses and perception. However, such tests have been difficult to conduct in rodents because current rodent visual testing methods or devices either do not allow accurate quantitative assessment for PLR or OKR or use subjective measures to score visual responses. To address these challenges, we propose to advance the technology by designing an easy-to-use automated platform that employs an eye/pupil tracking device equipped with a computer vision system (chiefly the interactive tracking system) for unambiguous objective scoring of visual responses. Our proposed new device will allow real-time quantitative and accurate assessment of rodent visual function including light responses, visual acuity and contrast sensitivity. The novelty of our system also lies in that it does not require complicated calibration procedures needed in commonly used human eye tracking. Rather than precisely measuring the extent of eye turning (or orientation), we propose to detect the signature eye movement in accordance with the speed and direction of visual stimuli. The system will be validated using normal wildtype mice and mouse models of retinal neurodegeneration known to develop visual behavior changes in the parameters mentioned above. Although rodent eye tracking has been investigated before, this proposed visual assessment system would be the first commercially viable product that uses an eye/pupil tracking device to automatically assess visual perception in rodents. The combined PLR and OKR tests and vastly simplified and automated quantification methods will also provide the first scalable behavior platform for phenotyping and drug discovery in the vision research area. In the future, this technology has the potential of being expanded to measure responses from various visual stimuli. This may translate into broader applications for evaluating brain diseases that afflict the visual pathways. This platform for mouse visual behavior assessment will therefore greatly facilitate drug discovery and development aimed at preventing and slowing vision loss or restoring sight, helping to combat devastating blinding conditions such as age-related macular degeneration (AMD) and glaucoma.
The objective of the current proposal is to design and develop an automated system for the measure of rodent (mice and rats) light response, visual acuity, and contrast sensitivity. The system will apply human eye/pupil tracking techniques for objective and unambiguous evaluation of light response and visual perception. This platform will provide a powerful tool for phenotypic studies as well as for discovery of new drugs that can prevent or restore sight caused by blinding conditions such as age-related macular degeneration and glaucoma.
