This project is to develop and support three state-of-the-art optical instruments that provide microscopic access to the living retina, and use them to obtain a clearer understanding of how the human visual system works. They will be used to answer questions about the most important and the most challenging region in the retina to study, the fovea. The instruments are built upon two key technical strengths - adaptive optics scanning laser ophthalmoscope (AOSLO) systems and accurate, high-speed eye-motion tracking. Adaptive optics (AO) technology corrects the imperfections in the eye and can be used to generate microscopic views of the living retina. AO also enables the delivery of ultra-sharp images to the retina. Eye tracking is used to measure and compensate for ever-present eye motion. Together, these allow for accurate visualization, tracking and delivery of light to retinal features as small as single cone photoreceptors, enabling measurements of properties of spatial and color vision on an unprecedented scale. Although the three systems will be identical and will be used to test vision on a cellular scale, the scope of study for each system will be very different. The AOSLO at the University of Alabama, Birmingham will be used to test vision in primates, the AOSLO at the University of California, Berkeley will be used to perform advanced vision testing on healthy human eyes, and the AOSLO at the University of California, San Francisco will be used to study patients with eye disease. The key advantage of having the BRP manage three identical systems is that it will facilitate hardware innovations plus rapid translation of knowledge and innovative testing from animal models to the clinic. Briefly, the specific aims are:
Aim 1 : Develop and deploy state-of-the-art AOSLO systems at each site. Demonstrate performance by performing objective densitometry measures in monkeys and humans to map the three classes of cone photoreceptor that subserve color vision.
Aim 2 : Develop improved eye tracking and stimulus delivery capabilities in each system. Confirm performance by using subjective psychophysical tests to map the same three classes of cone photoreceptor as in Aim 1.
Aim 3 : Perform a series of experiments in monkeys and humans to map the connections and interactions within and between the retina and the brain and to study how we see the world as stable even though our eyes are in constant motion.
Aim 4 : Apply advanced vision testing methods in the clinic to discover mechanisms for cone death in different diseases, to monitor changes in cone function and structure during disease progression and to test the efficacy of treatments that aim to stop or slow disease progression.
Aim 5 : Make eye tracking and targeted stimulus delivery capabilities accessible to a wider audience by providing software, hardware designs and a forum for anyone interesting in building similar advanced systems.

Public Health Relevance

The Bioengineering Research Partnership proposes to develop three state-of-the-art systems that enable the study of vision in living eyes on a cellular level. By deploying and using these systems in three environments - vision testing in animal models, vision testing in healthy normal eyes and vision testing in patients - we outline an effective strategy for answering long-standing questions about foveal vision, and also provide a means for efficient translation of technology into clinical applicability.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY023591-05
Application #
9479163
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Greenwell, Thomas
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Ophthalmology
Type
Schools of Optometry/Opht Tech
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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Ratnam, Kavitha; Domdei, Niklas; Harmening, Wolf M et al. (2017) Benefits of retinal image motion at the limits of spatial vision. J Vis 17:30
Tuten, William S; Harmening, Wolf M; Sabesan, Ramkumar et al. (2017) Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina. J Neurosci 37:9498-9509
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Winter, Simon; Sabesan, Ramkumar; Tiruveedhula, Pavan et al. (2016) Transverse chromatic aberration across the visual field of the human eye. J Vis 16:9
Sabesan, Ramkumar; Schmidt, Brian P; Tuten, William S et al. (2016) The elementary representation of spatial and color vision in the human retina. Sci Adv 2:e1600797
Sabesan, Ramkumar; Hofer, Heidi; Roorda, Austin (2015) Characterizing the Human Cone Photoreceptor Mosaic via Dynamic Photopigment Densitometry. PLoS One 10:e0144891

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