Mechanisms of Transport and Delivery of Vitamin A and Carotenoids to the Retinal Pigment Epithelium
Open accessAbstract
Vision depends on the delivery of vitamin A (retinol) to the retina. Retinol in blood is bound to retinol-binding protein (RBP). Retinal pigment epithelia (RPE) cells express the RBP receptor, STRA6, that facilitates uptake of retinol. The retinol is then converted to retinyl esters by the enzyme lecithin:retinol acyltransferase. The esters are the substrate for RPE65, an enzyme that produces 11-cis retinol, which is converted to 11-cis retinaldehyde for transport to the photoreceptors to form rhodopsin. The dietary xanthophylls, lutein (LUT) and zeaxanthin (ZEA), accumulate in the macula of the eye, providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the RPE. In blood, xanthophylls and β-carotene mostly associate with high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively. Studies using a human RPE cell model evaluate the kinetics of cell uptake when carotenoids are delivered in LDL or HDL. For LUT and β-carotene, LDL delivery result in the highest rate of uptake. HDL is more effective in delivering ZEA (and meso-ZEA). This selective HDL-mediated uptake of ZEA, via a scavenger receptor and LDL-mediated uptake of LUT and β-carotene provides a mechanism for the selective accumulation of ZEA > LUT and xanthophylls over β-carotene in the macula.
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Complex machinery of transporters and enzymes is involved in the visual cycle.
“Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle).”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
In visual phototransduction, large quantities of vitamin A in the form of 11-cis-retinal are isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal.
“In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
All-trans-retinal is continuously recycled back to 11-cis-retinal in the process called the visual cycle.
“The all-trans-retinal is continuously recycled back to the 11-cis-retinal in the process called the visual cycle.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
All-trans-retinal is converted to all-trans-retinol by all-trans-retinol dehydrogenases RDH8 in the outer segments and RDH12 in the inner segments of the photoreceptors.
“All-trans-retinal is released into the cytoplasm, where it can be converted to all-trans-retinol by all-trans-retinol dehydrogenases, RDH8 in the outer segments of the photoreceptors and RDH12 in the inner segments of the photoreceptors.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
IRBP helps transfer all-trans-retinol from photoreceptors to the RPE, where it can be converted back to 11-cis-retinal by LRAT, RPE65, RDH5 and RDH11.
“The IRBP helps transfer all-trans-retinol from photoreceptors to the RPE, where it can be converted back to 11-cis-retinal by the LRAT, RPE65, RDH5 and RDH11 enzymes as described above.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
The classical, or canonical, visual cycle involves regeneration of 11-cis-retinal in the RPE.
“The classical, or canonical visual cycle involves regeneration of 11-cis-retinal in the RPE.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
RPE65 is an isomerohydrolase that catalyses hydrolysis of esters and isomerizes all-trans-retinol to 11-cis-retinol.
“RPE65 is an isomerohydrolase that catalyses hydrolysis of esters and isomerizes all-trans-retinol to 11-cis-retinol [29,32,46].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
When all-trans-retinal is released from opsin, it binds phosphatidylethanolamine to form N-retinylidene-phosphatidylethanolamine, which is transported by ABCA4 across the membrane to the cytoplasmic side of the photoreceptor.
“When the all-trans-retinal is released from the opsin, on the luminal side of the photoreceptor membrane of rod discs and extracellular side in cones, it binds to the phosphatidylethanolamine to form N-retinylidene-phosphatidylethanolamine. The latter is transported by the ATP-binding cassette subfamily A member 4 transporter (ABCA4) across the membrane to the cytoplasmic side of the photoreceptor”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [32]
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References 65 · Cited by 97
- Authors
- Harrison, E. H.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Harrison, Earl H.
- ORCID
- Harrison, Earl H.
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2019-02-14
- Volume
- 63
- Issue
- 15
- Pages
- e1801046-e1801046
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2912941728
- Cited by
- 97
- References
- 65
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 10 · 2023: 11 · 2022: 20 · 2021: 13 · 2020: 12 · 2019: 7
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01‐DK044498)
- National Heart, Lung, and Blood Institute (R01‐HL049867)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin A transport, retinal pigment epithelium, carotenoid delivery, xanthophylls, lutein, zeaxanthin, beta-carotene, retinol-binding protein, STRA6, LRAT, RPE65, 11-cis-retinol, macula, age-related macular degeneration, high-density lipoprotein, low-density lipoprotein, scavenger receptors
- MeSH terms
- Animals, Carotenoids, Diet, Humans, Intestinal Absorption, Lipoproteins, HDL, Lipoproteins, LDL, Vitamin A, Retinal Pigment Epithelium
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