Interphotoreceptor Retinoid-Binding Protein as the Physiologically Relevant Carrier of 11-cis-Retinol in the Cone Visual Cycle
Open accessAbstract
Cones function in constant light and are responsible for mediating daytime human vision. Like rods, cones use the photosensitive molecule 11-cis-retinal to detect light, and in constant illumination, a continuous supply of 11-cis-retinal is needed. A retina visual cycle is thought to provide a privileged supply of 11-cis-retinal to cones by using 11-cis-retinol generated in Müller cells. In the cycle, 11-cis-retinol is transported from Müller cells to cone inner segments, where it is oxidized to 11-cis-retinal. This oxidation step is only performed in cones, thus rendering the cycle cone-specific. Interphotoreceptor retinoid-binding protein (IRBP) is a retinoid-binding protein in the subretinal space that binds 11-cis-retinol endogenously. Cones in Irbp−/−mice are retinoid-deficient under photopic conditions, and it is possible that 11-cis-retinol supplies are disrupted in the absence of IRBP. We tested the hypothesis that IRBP facilitates the delivery of 11-cis-retinol to cones by preserving the isomeric state of 11-cis-retinol in light. With electrophysiology, we show that the cone-like photoreceptors of Nrl−/−mice use the cone visual cycle similarly to wild-type cones. Then, using oxidation assays in isolated Nrl−/−Rpe65−/−retinas, we show that IRBP delivers 11-cis-retinol for oxidation in cones and improves the efficiency of the oxidation reaction. Finally, we show that IRBP protects the isomeric state of 11-cis-retinol in the presence of light. Together, these findings suggest that IRBP plays an important role in the delivery of 11-cis-retinol to cones and can facilitate cone function in the presence of light.
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In isolated Nrl-/-Rpe65-/- retinas, IRBP supplies 11-cis retinol to cones for oxidation and makes that oxidation more efficient.
“Using isolated Nrl-/-Rpe65-/-retinas, IRBP was shown to deliver 11-cis retinol for oxidation in cones and to enhance the efficiency of the oxidation reaction (Parker et al., 2011).”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Parker et al., 2011
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- Authors
- Parker, R., Wang, J.-S., Kefalov, V. J., & Crouch, R. K.
- Affiliations
- Medical University of South Carolina (US)
- Washington University in St. Louis (US)
- ORCID
- Kefalov, Vladimir J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-23
- Volume
- 31
- Issue
- 12
- Pages
- 4714-4719
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3226706
- OpenAlex
- W1986629963
- Cited by
- 49
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2020: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Foundation Fighting Blindness
- Research to Prevent Blindness (EY002687)
- Medical University of South Carolina
- University of South Carolina
- National Institutes of Health (EY002687)
- National Eye Institute (EY04939, R24EY014793, P30EY002687, R01EY019312, EY019312, EY002687, R01EY004939)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- interphotoreceptor retinoid-binding protein, 11-cis-retinol, 11-cis-retinal, Müller cells, cone photoreceptors, photoisomerization
- MeSH terms
- Retinoid Isomerohydrolase, Retinol-Binding Proteins, Interstitial, Animals, Carrier Proteins, Chromatography, High Pressure Liquid, Electroretinography, Eye Proteins, Light, Oxidation-Reduction, Retinoids, Retinol-Binding Proteins, Vision, Ocular, Vitamin A, Retinal Cone Photoreceptor Cells, Mice, Knockout, cis-trans-Isomerases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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