March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Phototransduction Gain Is Increased In Rods Overexpressing GARP2
Author Affiliations & Notes
  • Alex S. McKeown
    Vision Sciences, University of Alabama at Birmingham, Birmingham, Alabama
  • Shanta S. Sarfare
    Ophthalmology, Jules Stein Eye Institute, Los Angeles, California
  • Steven J. Pittler
    Vision Sciences, University of Alabama at Birmingham, Birmingham, Alabama
  • Timothy W. Kraft
    Vision Sciences, University of Alabama at Birmingham, Birmingham, Alabama
  • Footnotes
    Commercial Relationships  Alex S. McKeown, None; Shanta S. Sarfare, None; Steven J. Pittler, None; Timothy W. Kraft, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 755. doi:
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    • Get Citation

      Alex S. McKeown, Shanta S. Sarfare, Steven J. Pittler, Timothy W. Kraft; Phototransduction Gain Is Increased In Rods Overexpressing GARP2. Invest. Ophthalmol. Vis. Sci. 2012;53(14):755.

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

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Abstract

Purpose: : GARP2, a soluble glutamic acid and proline rich photoreceptor-specific protein has been linked to rod structure and disk morphogenesis. The protein is also known to associate with PDE6 (Pentia et al., 2006) and as such could have a physiological role. We previously showed using ERG analysis that transgenic mice over-expressing GARP2 by two-fold (GARP2 Tg) exhibit phototransduction gain 50-80% higher than that of wild-type animals. Here we compare the in vivo ERG results with alternative techniques that more specifically isolated rod photoreceptor electrical responses which provide strong supporting evidence for a role of GARP2 in phototransduction.

Methods: : Isolated photoreceptor currents and voltages were recorded from retinas or single cells of wild type and GARP2-Tg animals. Light stimuli varied from intensities that evoked minimum threshold responses up to those producing saturating responses. En masse recordings from a population of photoreceptors (ex-vivo ERG) were conducted by pharmacologically isolating the a-wave in the isolated retina. Single cell recordings were made using suction electrodes.

Results: : In both preparations, the rising phase of the responses were analyzed using a rod model of gain (Lamb & Pugh, 1992). Both the isolated retina preparation (n=2 WT; n=3 GARP-Tg) and single cell photoreceptors (n=7 WT; n=4 GARP2 Tg) demonstrated significantly higher gain in the GARP2 Tg mice. While the single cell results were more modest (25% gain increase) the GARP2 Tg isolated retinas showed a 3-fold increase in gain. The dominant time constant of the photoresponse recovery, a measure of PDE6 inactivation rate, was also significantly increased in the transgenic animals.

Conclusions: : Two-fold overexpression of GARP2 increases phototransduction gain, and delays recovery by increasing the dominant time constant. One plausible explanation is that an abundance of GARP2, through interactions with PDE6-gamma facilitates binding of T-αGTP, increasing gain, and inhibiting interactions of the RGS9 complex with activated PDE6. Our results indicate a role for GARP2 in modulating phototransduction.

Keywords: photoreceptors • signal transduction • electrophysiology: non-clinical 
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