Advanced Technology to Study Visual Function on a Cellular Scale

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Project Summary 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.