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Featured ArticleArticles, Cellular/Molecular

The Role of Interphotoreceptor Retinoid-Binding Protein on the Translocation of Visual Retinoids and Function of Cone Photoreceptors

Minghao Jin, Songhua Li, Steven Nusinowitz, Marcia Lloyd, Jane Hu, Roxana A. Radu, Dean Bok and Gabriel H. Travis
Journal of Neuroscience 4 February 2009, 29 (5) 1486-1495; DOI: https://doi.org/10.1523/JNEUROSCI.3882-08.2009
Minghao Jin
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Songhua Li
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Steven Nusinowitz
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Marcia Lloyd
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Jane Hu
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Roxana A. Radu
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Dean Bok
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Gabriel H. Travis
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Abstract

The first event in light perception is absorption of a photon by the retinaldehyde chromophore of an opsin pigment in a rod or cone photoreceptor cell. This induces isomerization of the chromophore, rendering the bleached pigment insensitive to light. Restoration of light sensitivity requires chemical reisomerization of retinaldehyde via a multistep enzyme pathway, called the visual cycle, in cells of the retinal pigment epithelium (RPE). Interphotoreceptor retinoid-binding protein (IRBP) is present in the extracellular space between photoreceptors and the RPE. IRBP is known to bind visual retinoids. Previous studies on irbp −/− mice suggested that IRBP plays an insignificant role in opsin-pigment regeneration. However, the mice in these studies were uncontrolled for a severe mutation in the rpe65 gene. Rpe65 catalyzes the rate-limiting step in the visual cycle. Here, we examined the phenotype in irbp −/− mice homozygous for the wild-type (Leu450) rpe65 gene. We show that lack of IRBP causes delayed transfer of newly synthesized chromophore from RPE to photoreceptors. Removal of bleached chromophore from photoreceptors is also delayed in irbp −/− retinas after light exposure. It was previously shown that rods degenerate in irbp −/− mice. Here, we show that cones and rods degenerate at similar rates. However, cones are more affected functionally and show greater reductions in outer segment length than rods in irbp −/− mice. The disproportionate reductions in cone function and outer-segment length appear to result from mistrafficking of cone opsins due to impaired delivery of retinaldehyde chromophore, which functions as a chaperone for cone opsins but not rhodopsin.

  • opsin
  • pigment epithelium
  • retinal degeneration
  • trafficking
  • visual cycle
  • vitamin A
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The Journal of Neuroscience: 29 (5)
Journal of Neuroscience
Vol. 29, Issue 5
4 Feb 2009
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The Role of Interphotoreceptor Retinoid-Binding Protein on the Translocation of Visual Retinoids and Function of Cone Photoreceptors
Minghao Jin, Songhua Li, Steven Nusinowitz, Marcia Lloyd, Jane Hu, Roxana A. Radu, Dean Bok, Gabriel H. Travis
Journal of Neuroscience 4 February 2009, 29 (5) 1486-1495; DOI: 10.1523/JNEUROSCI.3882-08.2009

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The Role of Interphotoreceptor Retinoid-Binding Protein on the Translocation of Visual Retinoids and Function of Cone Photoreceptors
Minghao Jin, Songhua Li, Steven Nusinowitz, Marcia Lloyd, Jane Hu, Roxana A. Radu, Dean Bok, Gabriel H. Travis
Journal of Neuroscience 4 February 2009, 29 (5) 1486-1495; DOI: 10.1523/JNEUROSCI.3882-08.2009
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