The research proposed for this award will examine functional and structural properties of single cells in the human retina. The three Aims will link the candidate's scientific background and career plans to study the human retina using a combination of adaptive optics (AO) and optical coherence tomography (OCT) which provide high lateral and high axial resolution, respectively (~2.5 ?m in all three dimensions).
Aim 1 will use AO-OCT to determine how the microscopic structure of the photoreceptors gives rise to the bands of the outer retina visible in routine clinical images-bands whose anatomical origins are not known precisely. It will test the hypothesis about whether the third band is from multiple reflectors in the interdigitation zone of the RPE or the tips of individual photoreceptors.
Aim 1 will also test hypotheses about the contributions of rods and S-cones to the OCT image.
Aim 2 will exploit this knowledge to noninvasively measure function in single photoreceptors, and identify a subset of cones, putative S-cones, often thought to be the first cone type to be affected by outer retinal disease.
Aim 3 will study the optical properties of the Mller cells whih are known to sustain retinal cells, and have been proposed, controversially, to also act as optical fibers for guiding light to the photoreceptors.
This Aim will test ideas about Mller cell wave-guiding properties, for the first time, in the living retina. The optical signatures of all ofthe retinal layers studied in each of the three Aims are seen in clinical OCT images, but their cellula origins are uncertain. The proposed research will thus provide data fundamental to understanding retinal structure and function, and will enrich our understanding of clinical OCT images of retinal disease. During the mentored phase of this Award, the candidate will draw on all phases of his previous vision science experience including adaptive optics and computational analysis of the 3D structure of retinal images, and will expand this experience in significant ways needed for his career plans. This work will be conducted in the laboratory of John S. Werner where AO-OCT instrumentation has been pioneered and conveniently located in the UC Davis Eye Center. One AO-OCT system is available for the candidate's modification and exclusive use. Training will be buttressed by mentoring and didactic courses with advisors, Edward N. Pugh, Jr. and Lawrence S. Morse, who are internationally renowned basic and clinical vision scientists, respectively. Additional didactic components include a 'Fluorescein' course normally taken by residents and fellows in Ophthalmology and a grant-writing course. The training provided through this K99 will set the stage for the candidate's independent career in vision science research.

Public Health Relevance

Human vision begins when light is captured by photoreceptor cells in the retina, and many blinding diseases of the eye begin when these cells degenerate or fail to function. The purpose of this project is to use cutting-edge optical and computational methods to study the structure and function of photoreceptors and the cells that sustain them. This research will produce fundamental knowledge about how human vision works, much of which will have direct implications for diagnosis and treatment of human eye disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Career Transition Award (K99)
Project #
5K99EY026068-02
Application #
9195103
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Agarwal, Neeraj
Project Start
2016-01-01
Project End
2017-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Davis
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Jonnal, Ravi S; Gorczynska, Iwona; Migacz, Justin V et al. (2017) The Properties of Outer Retinal Band Three Investigated With Adaptive-Optics Optical Coherence Tomography. Invest Ophthalmol Vis Sci 58:4559-4568
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
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