Human vision operates over a billion-fold range of light intensities ranging from starlight to bright daylight, with night vision subserved by retinal rod photoreceptor cells, and day vision by cone photoreceptor cells. Rods and cones mediate the first steps in vision by capturing light in their G-protein coupled receptors Rhodopsin, and L/M and S-cone opsins, respectively, whose activation then generates electrical responses through homologous G-protein-coupled receptor signaling cascades. While the molecular mechanisms that underlie the rod's ability to signal in dim light are now well understood, the mechanisms that enable some cones (but not rods) to function in bright daylight are relatively poorly understood. Using non-invasive optical and electroretinographic methodology applicable to humans, the proposed work proposed will investigate cone and rod function in vivo under daylight conditions, testing hypotheses about the mechanisms that allow cones expressing only M-opsin to operate in bright light, while cones expressing only S-opsin, and rods do not, and to understand how the very abundant, non- signaling rods cope with the enormous stress that daylight makes on their molecular machinery. Among key resources for the project are cone-monochromat mice created by the author and his collaborators, which only express one cone opsin, and adaptive-optics (AO) optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) customized and calibrated for precisely controlling the quantity of light captured by each of the mouse opsins. The work in this project addresses a fundamental need for in vivo studies of cone and rod function in daylight conditions, to establish cellular and molecular mechanistic foundations that support and interpret the signal advances in AO imaging of human cones and rods.

Public Health Relevance

! This research will provide a fundamental mechanistic understanding of photoreceptor function in the living eye under daytime conditions, and as such addresses objectives of the Retinal Diseases Panel (https://www.nei.nih.gov/sites/default/files/nei-pdfs/VisionResearch2012.pdf), which include investigating the ?mechanisms underlying light adaptation and recovery? and ?understand(ing) the molecular mechanisms and pathways in cone photoreceptors that have not been studied as extensively as (those of) rods.? The work develops and employs non-invasive optical technologies for assessing photoreceptor function in vivo in animal models, to advance the mechanistic understanding of human photoreceptor optical imaging.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002660-41
Application #
10104498
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Neuhold, Lisa
Project Start
1978-08-01
Project End
2022-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
41
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of California Davis
Department
Physiology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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