The adaptive optics scanning laser ophthalmoscope (AOSLO) is a custom-built tool used to overcome the limitations imposed by the eye's imperfect optics, allowing the researcher to noninvasively image individual cone photoreceptors in the living human retina. In addition to its capacity for high-resolution imaging, AOSLO can be employed to conduct aberration-free measures of visual sensitivity on a microscopic scale. Incorporating high-speed eye tracking into the AOSLO allows the visual stimulus to be targeted to retinal regions of interest with single cone precision. As a result, the AOSLO affords the best possible level of control over the visual stimulus, allowing highly precise correlations between retinal structure and function to be established.
The aim of this project is to develop tools-namely, AOSLO-based microperimetry-to enhance our understanding of the high-resolution structural information available in AOSLO images, and to apply these tools to the longitudinal study of structure-function relationships in patients with inherited retinal degenerations. AOSLO-based retinal imaging has shown potential as a highly-sensitive measure for disease progression in clinical trials evaluating outer retinal degenerations and their treatments A recent study from our group that included AOSLO imaging in a subset of three retinitis pigmentosa (RP) patients demonstrated that treatment with ciliary neurotrophic factor (CNTF) prevents photoreceptor loss relative to untreated eyes;however, the standard functional outcome measures used in the trial indicated no significant difference in visual performance between treated and untreated eyes. Because of its unprecedented ability to test visual sensitivity with high retinotopic precision, AOSLO-based microperimetry is uniquely suited to better elucidate the functional status of these CNTF-preserved cones. The proposed research aims to establish AOSLO-based microperimetry as a means to measure visual function on a microscopic scale. Once our optical set-up is optimized (Aim 1) and a normative database of AOSLO-based microperimetry values is established (Aim 2), we plan to apply these tools to examine the relationship between high-resolution retinal structure and function in patients with RP, including those undergoing CNTF treatment (Aims 3 and 4). The proposed project encompasses aspects of my previous research experiences, and has been designed to leave me with a unique set of skills that will put me on track to achieve my long-term goal of becoming an independent clinician-scientist conducting meaningful patient-based research. My mentor, Austin Roorda, offers expertise in developing advanced ophthalmic imaging systems, and my co-mentor, Jacque Duncan, brings experience in conducting patient-based research in patients with retinal degenerations. Their mentorship, combined with my career development plan and the support and facilities provided by UC Berkeley and UCSF, will position me to succeed in completing this project and achieving my career objectives.

Public Health Relevance

Adaptive optics scanning laser ophthalmoscopy (AOSLO) is a cutting-edge technology that can be modified to conduct simultaneous high-resolution imaging and functional testing of the cone photoreceptors in the living retina. The goal of the proposed study is to develop, validate, and implement AOSLO-based microperimetry in the study of high-resolution structure-function relationships in the retinas of normal subjects and patients with inherited retinal degenerations, which afflict approximately 100,000 people in the United States. AOSLO-based microperimetry has the capacity to precisely test the functional consequences of photoreceptor loss in patients with retinal disease, and it has the potential to become a sensitive tool for evaluating novel treatments aimed at slowing photoreceptor death.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1-VSN (06))
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Agarwal, Neeraj
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University of California Berkeley
Schools of Optometry/Ophthalmol
United States
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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
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
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
Bruce, Kady S; Harmening, Wolf M; Langston, Bradley R et al. (2015) Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors. Invest Ophthalmol Vis Sci 56:4431-8
Wang, Qinyun; Tuten, William S; Lujan, Brandon J et al. (2015) Adaptive optics microperimetry and OCT images show preserved function and recovery of cone visibility in macular telangiectasia type 2 retinal lesions. Invest Ophthalmol Vis Sci 56:778-86
Harmening, Wolf M; Tuten, William S; Roorda, Austin et al. (2014) Mapping the perceptual grain of the human retina. J Neurosci 34:5667-77