The role of interphotoreceptor retinoid-binding protein on the translocation of visual retinoids and function of cone photoreceptors
Open accessAbstract
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.
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The RPE65 isoform influences the Irbp-/- phenotype: the Leu450 variant was linked to shorter cone outer segments, mislocalized cone opsin, and progressive cone loss.
“The isoform of RPE65 appears to affect the phenotype of Irbp-/- mice as Jin et al. (Jin et al., 2009) reported cones in Irbp-/- mice with the Leu450 variant of RPE65 also had reduced outer segment length, partially mislocalized cone opsin, and underwent progressive degeneration.”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Jin et al., 2009
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The Cone-specific visual cycle
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“The isoform of RPE65 appears to affect the phenotype of Irbp / mice as Jin et al. (2009) reported cones in Irbp / mice with the Leu450 variant of RPE65 also had reduced outer segment length, partially mislocalized cone opsin, and underwent progressive degeneration.”
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Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease
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- Authors
- Jin, M., Li, S., Nusinowitz, S., Lloyd, M., Hu, J., Radu, R. A., Bok, D., & Travis, G. H.
- Affiliations
- Louisiana State University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Travis, Gabriel H.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-02-04
- Volume
- 29
- Issue
- 5
- Pages
- 1486-1495
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2680234
- OpenAlex
- W2022992728
- Cited by
- 109
- References
- 40
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 1 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 15 · 2014: 3 · 2013: 10 · 2012: 10
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation Fighting Blindness
- Research to Prevent Blindness
- National Eye Institute (R01EY015844, R01EY011713)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- interphotoreceptor retinoid-binding protein, visual cycle, cone photoreceptors, rod photoreceptors, RPE65, photoreceptor degeneration, outer segment length, rhodopsin
- MeSH terms
- Retinol-Binding Proteins, Interstitial, Animals, Cell Line, Eye Proteins, Humans, Photic Stimulation, Retinoids, Retinol-Binding Proteins, Retinal Cone Photoreceptor Cells, Mice, Knockout, Protein Transport, Mice
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