We are asking for support to continue to develop and enhance three state-of-the-art optical instruments that 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 technology corrects the imperfections in the eye and can be used to generate microscopic views of the living retina and deliver ultra-sharp images to the retina. Eye tracking is used to measure and compensate for ever-present eye motion. Together, these allow for 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, the scope of study for each system will be very different. The AOSLO at in Alabama will be used to test vision in non-human primates, the AOSLO in Berkeley will be used to perform advanced vision testing on healthy human eyes, and the AOSLO in 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 : Advanced AOSLO display capabilities for color vision: We propose a series of technical developments will expand the scope of AOSLO experiments, not just for color vision, but also spatial vision and clinical applications. Specifically, we will (i) add 2-photon stimulation (ii) develop new methods to display large stimuli that are fixed in world-coordinates (iii) integrate dichoptic displays to enable experiments that distinguish retinal from cortical visual processing (iv) develop I-TRACK (improved software tools for retina- contingent vision testing) and (v) invisible imaging and tracking. These tools will enable a series of experiments to learn how the visual system extracts color and spatial information from its sensory inputs.
Aim 2 : Enhanced AOSLO systems and modeling for spatial vision: In this aim we will (i) develop advanced wavefront propagation tools to model light-cone interactions (ii) integrate AOSLO microstimulation with a system for 2-photon functional brain imaging in non-human primates.
We aim to use these tools to greatly enhance our understanding of receptive fields at and near the fovea.
Aim 3 : Clinical translation: We will integrate the new technology into the system at UCSF to (i) study rod vision in patients with rod-cone degenerations (ii) measure the time course, structure and function of dysflective cones (iii) investigate the structure and function of the preferred retinal locus in diseases that affect the fovea and (iv) assess inner retinal function in eye disease.

Public Health Relevance

The Bioengineering Research Partnership proposes to develop and enhance capabilities of 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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Schools of Optometry/Opht Tech
United States
Zip Code
Foote, Katharina G; Loumou, Panagiota; Griffin, Shane et al. (2018) Relationship Between Foveal Cone Structure and Visual Acuity Measured With Adaptive Optics Scanning Laser Ophthalmoscopy in Retinal Degeneration. Invest Ophthalmol Vis Sci 59:3385-3393
Domdei, Niklas; Domdei, Lennart; Reiniger, Jenny L et al. (2018) Ultra-high contrast retinal display system for single photoreceptor psychophysics. Biomed Opt Express 9:157-172
Schmidt, Brian P; Boehm, Alexandra E; Foote, Katharina G et al. (2018) The spectral identity of foveal cones is preserved in hue perception. J Vis 18:19
Schmidt, Brian P; Sabesan, Ramkumar; Tuten, William S et al. (2018) Sensations from a single M-cone depend on the activity of surrounding S-cones. Sci Rep 8:8561
Agaoglu, Mehmet N; Sheehy, Christy K; Tiruveedhula, Pavan et al. (2018) Suboptimal eye movements for seeing fine details. J Vis 18:8
Lew, Young Ju; Rinella, Nicholas; Qin, Jia et al. (2018) High-resolution Imaging in Male Germ Cell-Associated Kinase (MAK)-related Retinal Degeneration. Am J Ophthalmol 185:32-42
Tuten, William S; Cooper, Robert F; Tiruveedhula, Pavan et al. (2018) Spatial summation in the human fovea: Do normal optical aberrations and fixational eye movements have an effect? J Vis 18:6
Tu, Joanna H; Foote, Katharina G; Lujan, Brandon J et al. (2017) Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis. Am J Ophthalmol Case Rep 7:14-19
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
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

Showing the most recent 10 out of 22 publications