Human vision starts when photoreceptors collect and respond to light. Normal photoreceptor function and structure are essential for normal vision, yet techniques to assess these in vivo are limited. Current optical and electrophysiological approaches have limited spatial resolution and sensitivity, and target only specific functional processes. New optical modalities that are rapid, specific, and non-invasive hold the promise of greatly expanding our capability to monitor more accurately and completely photoreceptor function and structure. We will use adaptive optics (AO) and spectral-domain optical coherence tomography (SD-OCT) to non-invasively image the human retina at the cellular scale. We will study the waveguide properties of photoreceptors, the interaction of fundus structure with wavefront sensing, and the phototransduction process.
The specific aims are to: (1.) Evaluate the anatomical origins and functional implications of optical waveguiding by photoreceptors in central and peripheral retina. This will be achieved in a hypothesis driven study using SD-OCT. (2.) Develop a quantitative optical model of the human fundus as a thick reflector that accounts for the impact of fundus structure on accuracy and precision of wavefront sensing. SD-OCT will be used to test the hypothesis that axial elongation and variation with pupil position of the fundus reflection leads to wavefront measurement errors if not controlled. (3.) Evaluate the potential of AO and SD-OCT as non-invasive, optical methods for measuring functional mechanisms of phototransduction by measuring light-evoked changes in the scattering properties of photoreceptors. The long term goal of this research is to establish advanced optical techniques for non-invasive probing of cellular function and structure in the human retina. These techniques will be used to study photoreceptors in vivo, and once established will promise improvements in early detection and treatment monitoring for diseases that impact these cells.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Neuhold, Lisa
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Indiana University Bloomington
Schools of Optometry/Ophthalmol
United States
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Kurokawa, Kazuhiro; Liu, Zhuolin; Miller, Donald T (2017) Adaptive optics optical coherence tomography angiography for morphometric analysis of choriocapillaris [Invited]. Biomed Opt Express 8:1803-1822
Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu et al. (2017) Imaging and quantifying ganglion cells and other transparent neurons in the living human retina. Proc Natl Acad Sci U S A 114:12803-12808
Marcos, Susana; Werner, John S; Burns, Stephen A et al. (2017) Vision science and adaptive optics, the state of the field. Vision Res 132:3-33
Liu, Zhuolin; Kocaoglu, Omer P; Miller, Donald T (2016) 3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina. Invest Ophthalmol Vis Sci 57:OCT533-43
Kocaoglu, Omer P; Liu, Zhuolin; Zhang, Furu et al. (2016) Photoreceptor disc shedding in the living human eye. Biomed Opt Express 7:4554-4568
Jonnal, Ravi S; Kocaoglu, Omer P; Zawadzki, Robert J et al. (2016) A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future. Invest Ophthalmol Vis Sci 57:OCT51-68
Jonnal, Ravi S; Kocaoglu, Omer P; Zawadzki, Robert J et al. (2015) Author Response: Outer Retinal Bands. Invest Ophthalmol Vis Sci 56:2507-10
Kocaoglu, Omer P; Turner, Timothy L; Liu, Zhuolin et al. (2014) Adaptive optics optical coherence tomography at 1 MHz. Biomed Opt Express 5:4186-200
Jonnal, Ravi S; Kocaoglu, Omer P; Zawadzki, Robert J et al. (2014) The cellular origins of the outer retinal bands in optical coherence tomography images. Invest Ophthalmol Vis Sci 55:7904-18
Kocaoglu, Omer P; Ferguson, R Daniel; Jonnal, Ravi S et al. (2014) Adaptive optics optical coherence tomography with dynamic retinal tracking. Biomed Opt Express 5:2262-84

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