June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Contribution of RGS proteins to the light responses of ON-bipolar neurons
Author Affiliations & Notes
  • Ignacio Sarria
    Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Kirill Martemyanov
    Neuroscience, The Scripps Research Institute, Jupiter, FL
  • Footnotes
    Commercial Relationships Ignacio Sarria, None; Kirill Martemyanov, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6160. doi:
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      Ignacio Sarria, Kirill Martemyanov; Contribution of RGS proteins to the light responses of ON-bipolar neurons. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6160.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Transmission of the light signal from rods to downstream ON-bipolar cells (ON-BC) is essential for dim vision and dysfunctions in components of this signaling pathway have been shown to result in night blindness in humans. In ON-BC the signaling is mediated by the G protein signal transduction cascade where the mGluR6 receptor constantly stimulated in the dark by glutamate activates Go and keeps the effector channel TRPM1 closed. Yet, how opening of TRPM1 is controlled and/or regulated is not well known. We have recently shown that RGS7 and RGS11 control Go deactivation and their complete knockout in mice eliminates ON-BC responses to light flashes and severely retard TRPM1 opening. Here, using an inducible knockout model of RGS7, we partially reduce the concentration of RGS proteins while evaluating the effect on visual phenotypes in mice.

Methods: Conditional line of RGS7 knockout (KO) mice on RGS11 KO background was bred with the driver line ubiquitously expressing tamoxifen-inducible Cre-ERT2 recombinase (cDKO mice). Knockout of RGS7 was induced by oral gavage and light responses of dark-adapted mice were analyzed by standard ERG, 12 and 17 days after tamoxifen administration. Retinas were collected at matching time points for RGS protein quantification by Western blotting and synaptic morphology characterization by immunohistochemistry.

Results: Delivery of tamoxifen for 17 days markedly reduced RGS7 levels as evidenced by Western blotting. Before tamoxifen, the ERG responses of cDKO mice were not different from those seen in RGS11 KO mice. Tamoxifen caused a progressive delay in the onset of the b-wave as well as a decrease in the steepness of the rising slope. At 12 days the implicit time of the response slowed to 114 ms and by 17 days reached 184 ms as compared to 65 ms before tamoxifen administration. Mice with complete absence of RGS proteins still showed b-wave response with 745 ms implicit time and very shallow slope. However, this b-wave no longer reflects the activity of the ON-BC as it was also present in mice lacking mGluR6 and TRPM1.

Conclusions: Inducible decrease of RGS7 protein results in a novel b-wave phenotype with severely retarded onset time and kinetics. These results point that titration of RGS concentration in ON-BC results in a graded regulation of the b-wave. We conclude that the RGS proteins in ON-BC modulate light responses in ON-BC by dynamically regulating TRPM1 channel opening.

Keywords: 510 electroretinography: non-clinical • 435 bipolar cells • 714 signal transduction  

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