June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Exchange Of Cone For Rod Phosphodiesterase 6 In Rod Photoreceptors Mimics Features Of Light Adaptation
Author Affiliations & Notes
  • Johan Pahlberg
    Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Anurima Majumder
    Dept. of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA
  • Hakim Muradov
    Dept. of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA
  • Kimberly Boyd
    Dept. of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA
  • Alapakkam P Sampath
    Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Nikolai Artemyev
    Dept. of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA
    Dept. of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA
  • Footnotes
    Commercial Relationships Johan Pahlberg, None; Anurima Majumder, None; Hakim Muradov, None; Kimberly Boyd, None; Alapakkam Sampath, None; Nikolai Artemyev, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1712. doi:
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      Johan Pahlberg, Anurima Majumder, Hakim Muradov, Kimberly Boyd, Alapakkam P Sampath, Nikolai Artemyev; Exchange Of Cone For Rod Phosphodiesterase 6 In Rod Photoreceptors Mimics Features Of Light Adaptation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1712.

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

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Abstract

Purpose: While phototransduction research has focused largely on rods due to their abundance and quantum sensitivity, much less is known about cones despite their importance for most of our visual experience. Rods and cones express homologous phototransduction components, but the molecular basis for differences in their light-evoked responses remains unclear. We examined the hypothesis that PDE6 isoforms are essential contributors to the distinct physiology of rods and cones.

Methods: We generated transgenic mice expressing cone PDE6 (PDE6C) in rd1/rd1 rods lacking functional rod PDE6 (PDE6AB). Double transgenic rods (PDE6C++) with two PDE6C alleles were compared to rd1/+ rods based on similar PDE6 expression. Whole-cell patch clamp and suction electrode recordings were used to record the membrane current from rod photoreceptors in dark-adapted mouse retina. In experiments to assess light adaptation, a second light-emitting diode’s output produced the background light.

Results: Our results show that PDE6C expression rescues rd1/rd1 rods from retinal degeneration. PDE6C increased the basal PDE activity and caused rods to display properties of light adaption, inclucing reduced dark current and light sensitivity, and faster light response kinetics. When PDE6C++ and rd1/+ rods were exposed to similar background light, the rd1/+ control rods displayed greater desensitization.

Conclusions: Our transgenic approach allowed uniform transgene expression and the monitoring of levels of PDE6C protein and activity. The results are consistent with the increased spontaneous activity of PDE6C compared to PDE6AB in darkness. The reduced desensitization in background light compared to the dark-adapted state is consistent with the less efficient amplification of PDE6C++ activity compared to PDE6AB. Thus, higher basal PDE6C activity partially accounts for the differences in cone versus rod photoresponses in darkness, whereas reduced activation of PDE6C in light may allow cones to avoid saturation in steady light and increase their operational range.

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