The absorption of photons in rods and cones of the retina activates a cascade of biochemical reactions (phototransduction cascade) that generates the electrical response to light. The activation and deactivation of the cascade ultimately limits the amplitude and kinetics of the transduced signal, and thus the sensitivity and temporal resolution of vision. The overall goal of this study is to understand the mechanisms that turn off the light response in intact mouse photoreceptors. Gene targeting techniques will be used to manipulate the function of a subset of proteins that have been suggested to play key roles in deactivation of the cascade, and the resulting changes in the photoresponses of single rod cells will be determined by electrical recording. Using this approach, we will address 3 important questions: (1) How rapidly does rhodopsin become phosphorylated, and what determines this time course? (2) What are the functional consequences of arrestin translocation on the photoresponse? (3) Are the photoreceptor-specific splice variants of the RGS9 complex uniquely suited for deactivating transducin/PDE, and how? and 4) What are the mechanisms that speed transducin/PDE deactivation during light adaptation? This research addresses 1 of the objectives recommended by the Retinal Diseases Panel (www.nei.nih.gov/strategicplanning/np_retinal.asp#obj), which is to """"""""Analyze the mechanisms underlying light adaptation and recovery following phototransduction and understand the changes in neural coding in light/dark adaptation."""""""" This research will help clarify the initial steps in the normal visual process, as well as the pathogenesis of diseases that arise from failures of deactivation, such as in some forms of retinitis pigmentosa and nightblindness. In a broader context, these experiments will provide insights into the mechanisms of deactivation of G protein cascades, which all eucaryotic cells use to transduce extracellular signals into intracellular responses.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014047-09
Application #
7809498
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
2002-05-01
Project End
2011-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
9
Fiscal Year
2010
Total Cost
$365,291
Indirect Cost
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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
Burns, Marie E; Levine, Emily S; Miller, Eric B et al. (2016) New Developments in Murine Imaging for Assessing Photoreceptor Degeneration In Vivo. Adv Exp Med Biol 854:269-75
Zhang, Pengfei; Goswami, Mayank; Zam, Azhar et al. (2015) Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO. Opt Lett 40:5830-3
Fortenbach, Christopher R; Kessler, Christopher; Peinado Allina, Gabriel et al. (2015) Speeding rod recovery improves temporal resolution in the retina. Vision Res 110:57-67
Kessler, Christopher; Tillman, Megan; Burns, Marie E et al. (2014) Rhodopsin in the rod surface membrane regenerates more rapidly than bulk rhodopsin in the disc membranes in vivo. J Physiol 592:2785-97
Levine, Emily S; Zam, Azhar; Zhang, Pengfei et al. (2014) Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1. Vision Res 102:71-9
Arshavsky, Vadim Y; Burns, Marie E (2014) Current understanding of signal amplification in phototransduction. Cell Logist 4:e29390
Long, James H; Arshavsky, Vadim Y; Burns, Marie E (2013) Absence of synaptic regulation by phosducin in retinal slices. PLoS One 8:e83970
Gross, Owen P; Pugh Jr, Edward N; Burns, Marie E (2012) Spatiotemporal cGMP dynamics in living mouse rods. Biophys J 102:1775-84
Arshavsky, Vadim Y; Burns, Marie E (2012) Photoreceptor signaling: supporting vision across a wide range of light intensities. J Biol Chem 287:1620-6

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