Human vision starts when photoreceptors collect and respond to light. Normal photoreceptor function and its support from the underlying retinal pigment epithelium (RPE) are essential for normal vision, yet techniques to assess these processes in vivo are limited. Current optical and electrophysiological techniques have limited spatial resolution and sensitivity, and target only specific functional processes. New optical modalities that are rapid, specific, and noninvasive hold the promise of greatly expanding our capability to monitor more accurately and completely the photoreceptor RPE complex. We will use adaptive optics (AO) and optical coherence tomography (OCT) to achieve unprecedented 3D resolution for studying physiological mechanisms at the cellular level in the photoreceptor and RPE layers. Further improvements will be realized using AOOCT in conjunction with an exquisitely sensitive phase technique that we have developed and that measures optical length changes as small as 45nm.This is slightly thicker than a single cone outer segment (OS) disc and nearly 100times better than the axial resolution of ultra high resolution OCT.
The specific aims are to: (1) Determine the physical parameters that control light capture in photoreceptors;(2) Evaluate properties of light scatter in photoreceptors;and (3) Evaluate properties of light scatter in RPE.

Public Health Relevance

The long term goal of this research is to establish high-resolution imaging methods that probe structure and function of the retina at the cellular scale. The target cells in this study are photoreceptors and retinal pigment epithelial cells, both associated with the capture of light and the first step in seeing. As disease starts at the cellula and molecular levels, the ability to study these pathological disruptions at the single cell level and in patients promises improvements in early detection and treatment monitoring of some of the most blinding diseases in the world.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018339-07
Application #
8523882
Study Section
Special Emphasis Panel (NOIT)
Program Officer
Neuhold, Lisa
Project Start
2007-09-01
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2013
Total Cost
$354,540
Indirect Cost
$117,040
Name
Indiana University Bloomington
Department
Type
Schools of Optometry/Ophthalmol
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
South, Fredrick A; Kurokawa, Kazuhiro; Liu, Zhuolin et al. (2018) Combined hardware and computational optical wavefront correction. Biomed Opt Express 9:2562-2574
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
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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

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