Trial reportProceedings of the National Academy of Sciences of the United States of America2014
Inactivity of human β,β-carotene-9',10'-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Pooled it
- MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.Retina (Philadelphia, Pa.) · 2017Trial
- Review
- A regulatory 24-bp insertion at the BCO2 gene region is associated with yellow skin in chickens.Genetics, selection, evolution : GSE · 2026Article
- Carotenoid bioavailability in humans reflects the mammalian nocturnal bottleneck: a position paper.Journal of clinical biochemistry and nutrition · 2026Article
- Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice.Life (Basel, Switzerland) · 2025Article
- Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Article
- Imaging macular carotenoids and their related proteins in the human retina with confocal resonance Raman and fluorescence microscopy.Experimental eye research · 2024Article
- Functional Analysis of β-Carotene Oxygenase 2 (International journal of molecular sciences · 2024Article
- Utilization of Biopolymer-Based Lutein Emulsion as an Effective Delivery System to Improve Lutein Bioavailability in Neonatal Rats.Nutrients · 2024Article
- Potential roles of dietary zeaxanthin and lutein in macular health and function.Nutrition reviews · 2023Review
- Maternal High-Fat Diet Consumption in Sprague Dawley Rats Compromised the Availability and Altered the Tissue Distribution of Lutein in Neonatal Offspring.Metabolites · 2023Article
- Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI.Experimental eye research · 2023Article
- Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Nourishing Better Vision: The ARVO 2021 Mildred Weisenfeld Award Lecture.Investigative ophthalmology & visual science · 2022Article
- HDL is the primary transporter for carotenoids from liver to retinal pigment epithelium in transgenic ApoA-IArchives of biochemistry and biophysics · 2022Article
- Carotenoid modifying enzymes in metazoans.Methods in enzymology · 2022Article
- Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants.Nutrients · 2021Review
- Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4Experimental eye research · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The macula of the primate retina uniquely concentrates high amounts of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin, but the underlying biochemical mechanisms for this spatial- and species-specific localization have not been fully elucidated. For example, despite abundant retinal levels in mice and primates of a binding protein for zeaxanthin and meso-zeaxanthin, the pi isoform of glutathione S-transferase (GSTP1), only human and monkey retinas naturally contain detectable levels of these carotenoids. We therefore investigated whether or not differences in expression, localization, and activity between mouse and primate carotenoid metabolic enzymes could account for this species-specific difference in retinal accumulation. We focused on β,β-carotene-9',10'-dioxygenase (BCO2, also known as BCDO2), the only known mammalian xanthophyll cleavage enzyme. RT-PCR, Western blot analysis, and immunohistochemistry (IHC) confirmed that BCO2 is expressed in both mouse and primate retinas. Cotransfection of expression plasmids of human or mouse BCO2 into Escherichia coli strains engineered to produce zeaxanthin demonstrated that only mouse BCO2 is an active zeaxanthin cleavage enzyme. Surface plasmon resonance (SPR) binding studies showed that the binding affinities between human BCO2 and lutein, zeaxanthin, and meso-zeaxanthin are 10- to 40-fold weaker than those for mouse BCO2, implying that ineffective capture of carotenoids by human BCO2 prevents cleavage of xanthophyll carotenoids. Moreover, BCO2 knockout mice, unlike WT mice, accumulate zeaxanthin in their retinas. Our results provide a novel explanation for how primates uniquely concentrate xanthophyll carotenoids at high levels in retinal tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.