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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012155-16
Application #
8464114
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
2013-05-01
Budget End
2014-04-30
Support Year
16
Fiscal Year
2013
Total Cost
$575,742
Indirect Cost
$224,680
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
Wang, Tian; Chen, Jeannie (2014) Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells. J Biol Chem 289:29310-21
Hoyo, Natalia López-Del; López-Begines, Santiago; Rosa, Jose Luis et al. (2014) Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity. PLoS Genet 10:e1004480
Moaven, Hormoz; Koike, Yukihiro; Jao, Christine C et al. (2013) Visual arrestin interaction with clathrin adaptor AP-2 regulates photoreceptor survival in the vertebrate retina. Proc Natl Acad Sci U S A 110:9463-8
Mao, Wen; Miyagishima, K J; Yao, Yun et al. (2013) Functional comparison of rod and cone G*(t) on the regulation of light sensitivity. J Biol Chem 288:5257-67
Song, Xiufeng; Seo, Jungwon; Baameur, Faiza et al. (2013) Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant. Cell Signal 25:2613-24
Tsang, Stephen H; Woodruff, Michael L; Lin, Chyuan-Sheng et al. (2012) Effect of the ILE86TER mutation in the ? subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling. Cell Signal 24:181-8
Cleghorn, Whitney M; Tsakem, Elviche L; Song, Xiufeng et al. (2011) Progressive reduction of its expression in rods reveals two pools of arrestin-1 in the outer segment with different roles in photoresponse recovery. PLoS One 6:e22797
Blakeley, Lorie R; Chen, Chunhe; Chen, Ching-Kang et al. (2011) Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation. Invest Ophthalmol Vis Sci 52:3483-91
Song, X; Vishnivetskiy, S A; Seo, J et al. (2011) Arrestin-1 expression level in rods: balancing functional performance and photoreceptor health. Neuroscience 174:37-49
Kim, Yujin E; Chen, Jeannie; Langen, Ralf et al. (2010) Monitoring apoptosis and neuronal degeneration by real-time detection of phosphatidylserine externalization using a polarity-sensitive indicator of viability and apoptosis. Nat Protoc 5:1396-405

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