Chromophore supply rate-limits mammalian photoreceptor dark adaptation

J Neurosci. 2014 Aug 20;34(34):11212-21. doi: 10.1523/JNEUROSCI.1245-14.2014.

Abstract

Efficient regeneration of visual pigment following its destruction by light is critical for the function of mammalian photoreceptors. Here, we show that misexpression of a subset of cone genes in the rd7 mouse hybrid rods enables them to access the normally cone-specific retina visual cycle. The rapid supply of chromophore by the retina visual cycle dramatically accelerated the mouse rod dark adaptation. At the same time, the competition between rods and cones for retina-derived chromophore slowed cone dark adaptation, indicating that the cone specificity of the retina visual cycle is key for rapid cone dark adaptation. Our findings demonstrate that mammalian photoreceptor dark adaptation is dominated by the supply of chromophore. Misexpression of cone genes in rods may represent a novel approach to treating visual disorders associated with mutations of visual cycle proteins or with reduced retinal pigment epithelium function due to aging.

Keywords: dark adaptation; photoreceptors; pigment regeneration; retina; retinol dehydrogenase; visual cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Dark Adaptation / physiology*
  • Female
  • GTP-Binding Protein alpha Subunits / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroglia / physiology
  • Orphan Nuclear Receptors / genetics
  • Photic Stimulation*
  • Retina / cytology
  • Retina / radiation effects
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Rod Photoreceptor Cells / physiology*
  • Retinal Rod Photoreceptor Cells / radiation effects
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Time Factors
  • Transducin / genetics
  • Vitamin A / pharmacology
  • Vitamins / pharmacology

Substances

  • GTP-Binding Protein alpha Subunits
  • Gnat1 protein, mouse
  • Nr2e3 protein, mouse
  • Orphan Nuclear Receptors
  • Vitamins
  • Vitamin A
  • Rhodopsin
  • Transducin