Abstract

Retinal rods utilize a prototypical G-protein signaling cascade to encode our visual scene under dim light. Often, defects in the molecular components of this cascade, or their over-stimulation by bright light, cause blinding disorders in humans.
The first aim will investigate biochemical cascades in rods following bright light exposure that may slow dark adaptation.
The second aim i s to investigate the induction of endoplasmic stress by bright light exposure and mis-folded rhodopsin with the goal towards manipulation of these pathways to prolong photoreceptor cell survival. The long term objective of this proposal is to understand phototransduction in normal function and dysfunction so that this knowledge can be used to devise strategies for the treatment of human visual disorders.

Public Health Relevance

Photoreceptor cells utilize a prototypical G-protein signaling cascade to convey the presence of light. Genetic mutations and environmental factors that affect the performance of this signaling cascade cause many different forms of blinding diseases through mechanisms that are not well defined. A thorough understanding of these mechanisms will help in the design of treatment options.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY012155-15
Application #
8296223
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Neuhold, Lisa
Project Start
1998-03-01
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
15
Fiscal Year
2012
Total Cost
$602,705
Indirect Cost
$234,828

  Institution

Name
University of Southern California
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

LaVail, Matthew M; Nishikawa, Shimpei; Steinberg, Roy H et al. (2018) Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration. Exp Eye Res 167:56-90
Vinberg, Frans; Chen, Jeannie; Kefalov, Vladimir J (2018) Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors. Prog Retin Eye Res 67:87-101
Wang, Tian; Reingruber, Jürgen; Woodruff, Michael L et al. (2018) The PDE6 mutation in the rd10 retinal degeneration mouse model causes protein mislocalization and instability and promotes cell death through increased ion influx. J Biol Chem 293:15332-15346
Vinberg, Frans; Peshenko, Igor V; Chen, Jeannie et al. (2018) Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors. J Biol Chem 293:7457-7465
Vinberg, Frans; Wang, Tian; De Maria, Alicia et al. (2017) The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision. Elife 6:
Wang, Tian; Tsang, Stephen H; Chen, Jeannie (2017) Two pathways of rod photoreceptor cell death induced by elevated cGMP. Hum Mol Genet 26:2299-2306
Rose, Kasey; Walston, Steven T; Chen, Jeannie (2017) Separation of photoreceptor cell compartments in mouse retina for protein analysis. Mol Neurodegener 12:28
Lee, Amy S; Brandhorst, Sebastian; Rangel, Daisy F et al. (2017) Effects of Prolonged GRP78 Haploinsufficiency on Organ Homeostasis, Behavior, Cancer and Chemotoxic Resistance in Aged Mice. Sci Rep 7:40919
Cho, Jung-Hwa; Swanson, Carter J; Chen, Jeannie et al. (2017) The GCaMP-R Family of Genetically Encoded Ratiometric Calcium Indicators. ACS Chem Biol 12:1066-1074
Sakurai, Keisuke; Vinberg, Frans; Wang, Tian et al. (2016) The Na(+)/Ca(2+), K(+) exchanger 2 modulates mammalian cone phototransduction. Sci Rep 6:32521

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