Cone photoreceptor cells initiate vision in daytime, operating in light intensities that saturate rods and render them useless to the visual system. The ability of cones to escape saturation relies in large part upon specializations of proteins, including cone opsins, within the cone phototransduction cascade that function in synergy to preserve inward cGMP-sensitive current in strong light. During their biosynthesis, cone opsins have a surprising need for the visual chromophore, 11-cis retinal, to achieve proper folding, and our preliminary data suggests that they also possess a compensating capacity for proteolytic degradation of misfolded proteins. The proposed work will lead to a comprehensive, molecularly based account of these specializations within cones, and could be used in future work to both extend the operating range of the much more numerous rods, and develop strategies that facilitate the generation of properly folded opsins or increase the capacity to degrade misfolded opsins.

Public Health Relevance

This research will provide novel, fundamental insights into the mechanisms of daytime vision, and into the mechanisms that govern the normal folding of the proteins that initiate daytime vision, the cone opsins, whose misfolding is implicated in cone- and cone-rod dystrophies. This research addresses two of the objectives recommended by the Retinal Diseases Panel (http://www.nei.nih.gov/strategicplanning/np_retinal.asp#obj) of the NEI, which are to Use both molecular and physiological approaches to study light adaptation in photoreceptors, with particular emphasis on the visual cycle ... and Understand the cell biology of cones, including outer segment renewal and shedding, the phototransduction cascade, retinoid metabolism, opsin trafficking, and the regulation of gene expression for cone pigments. (http://www.nei.nih.gov/strategicplanning/np_retinal.asp)

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002660-36
Application #
8719106
Study Section
Biology and Diseases of the Posterior Eye (BDPE)
Program Officer
Neuhold, Lisa
Project Start
1978-08-01
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
36
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Davis
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Davis
State
CA
Country
United States
Zip Code
95618
Wang, Xinlei; Miller, Eric B; Goswami, Mayank et al. (2017) Rapid monocyte infiltration following retinal detachment is dependent on non-canonical IL6 signaling through gp130. J Neuroinflammation 14:121
Peinado Allina, Gabriel; Fortenbach, Christopher; Naarendorp, Franklin et al. (2017) Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9. J Gen Physiol 149:443-454
Zhang, Pengfei; Zawadzki, Robert J; Goswami, Mayank et al. (2017) In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors. Proc Natl Acad Sci U S A 114:E2937-E2946
Lu, Chen D; Lee, ByungKun; Schottenhamml, Julia et al. (2017) Photoreceptor Layer Thickness Changes During Dark Adaptation Observed With Ultrahigh-Resolution Optical Coherence Tomography. Invest Ophthalmol Vis Sci 58:4632-4643
Zhang, Pengfei; Goswami, Mayank; Zawadzki, Robert J et al. (2016) The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy. Invest Ophthalmol Vis Sci 57:3650-64
Bonora, Stefano; Jian, Yifan; Zhang, Pengfei et al. (2015) Wavefront correction and high-resolution in vivo OCT imaging with an objective integrated multi-actuator adaptive lens. Opt Express 23:21931-41
Zhang, Tao; Enemchukwu, Nduka O; Jones, Alex et al. (2015) Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse model of Leber congenital amaurosis. Hum Mol Genet 24:1755-63
Zhang, Pengfei; Zam, Azhar; Jian, Yifan et al. (2015) In vivo wide-field multispectral scanning laser ophthalmoscopy-optical coherence tomography mouse retinal imager: longitudinal imaging of ganglion cells, microglia, and Müller glia, and mapping of the mouse retinal and choroidal vasculature. J Biomed Opt 20:126005
Zawadzki, Robert J; Zhang, Pengfei; Zam, Azhar et al. (2015) Adaptive-optics SLO imaging combined with widefield OCT and SLO enables precise 3D localization of fluorescent cells in the mouse retina. Biomed Opt Express 6:2191-210
Gross, Owen P; Pugh Jr, Edward N; Burns, Marie E (2015) cGMP in mouse rods: the spatiotemporal dynamics underlying single photon responses. Front Mol Neurosci 8:6

Showing the most recent 10 out of 67 publications