{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:09:14Z","timestamp":1792789754211,"version":"4.5.0"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"NIH-NEI","doi-asserted-by":"publisher","award":["EY025034"],"award-info":[{"award-number":["EY025034"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH-NEI","doi-asserted-by":"publisher","award":["EY030889"],"award-info":[{"award-number":["EY030889"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH-NEI","doi-asserted-by":"publisher","award":["EY027013"],"award-info":[{"award-number":["EY027013"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH-NEI","doi-asserted-by":"publisher","award":["019898-001"],"award-info":[{"award-number":["019898-001"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NIH-NEI","doi-asserted-by":"publisher","award":["5UL1TR001450"],"award-info":[{"award-number":["5UL1TR001450"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DCI research","award":["EY025034"],"award-info":[{"award-number":["EY025034"]}]},{"name":"DCI research","award":["EY030889"],"award-info":[{"award-number":["EY030889"]}]},{"name":"DCI research","award":["EY027013"],"award-info":[{"award-number":["EY027013"]}]},{"name":"DCI research","award":["019898-001"],"award-info":[{"award-number":["019898-001"]}]},{"name":"DCI research","award":["5UL1TR001450"],"award-info":[{"award-number":["5UL1TR001450"]}]},{"name":"University of Minnesota start-up funds","award":["EY025034"],"award-info":[{"award-number":["EY025034"]}]},{"name":"University of Minnesota start-up funds","award":["EY030889"],"award-info":[{"award-number":["EY030889"]}]},{"name":"University of Minnesota start-up funds","award":["EY027013"],"award-info":[{"award-number":["EY027013"]}]},{"name":"University of Minnesota start-up funds","award":["019898-001"],"award-info":[{"award-number":["019898-001"]}]},{"name":"University of Minnesota start-up funds","award":["5UL1TR001450"],"award-info":[{"award-number":["5UL1TR001450"]}]},{"name":"SCTR-NIH\/NCATS","award":["EY025034"],"award-info":[{"award-number":["EY025034"]}]},{"name":"SCTR-NIH\/NCATS","award":["EY030889"],"award-info":[{"award-number":["EY030889"]}]},{"name":"SCTR-NIH\/NCATS","award":["EY027013"],"award-info":[{"award-number":["EY027013"]}]},{"name":"SCTR-NIH\/NCATS","award":["019898-001"],"award-info":[{"award-number":["019898-001"]}]},{"name":"SCTR-NIH\/NCATS","award":["5UL1TR001450"],"award-info":[{"award-number":["5UL1TR001450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The systemic transport of dietary vitamin A\/all-trans retinol bound to RBP4 into peripheral tissues for storage is an essential physiological process that continuously provides visual chromophore precursors to the retina under fasting conditions. This mechanism is critical for phototransduction, photoreceptor cell maintenance and survival, and in the support of visual function. While the membrane receptor STRA6 facilitates the blood transport of lipophilic vitamin A into the eye, it is not expressed in most peripheral organs, which are proposed to express a second membrane receptor for the uptake of vitamin A from circulating RBP4. The discovery of a novel vitamin A receptor, RBPR2, which is expressed in the liver and intestine, but not in the eye, alluded to this long-sort non-ocular membrane receptor for systemic RBP4-ROL uptake and transport. We have previously shown in zebrafish that the retinol-binding protein receptor 2 (Rbpr2) plays an important role in the transport of yolk vitamin A to the eye. Mutant rbpr2 zebrafish lines manifested in decreased ocular retinoid concentrations and retinal phenotypes. To investigate a physiological role for the second vitamin A receptor, RBPR2, in mammals and to analyze the metabolic basis of systemic vitamin A transport for retinoid homeostasis, we established a whole-body Rbpr2 knockout mouse (Rbpr2\u2212\/\u2212) model. These mice were viable on both vitamin A-sufficient and -deficient diets. Rbpr2\u2212\/\u2212 mice that were fed a vitamin A-sufficient diet displayed lower ocular retinoid levels, decreased opsins, and manifested in decrease visual function, as measured by electroretinography. Interestingly, when Rbpr2\u2212\/\u2212 mice were fed a vitamin A-deficient diet, they additionally showed shorter photoreceptor outer segment phenotypes, altogether manifesting in a significant loss of visual function. Thus, under conditions replicating vitamin A sufficiency and deficiency, our analyses revealed that RBPR2-mediated systemic vitamin A transport is a regulated process that is important for vitamin A delivery to the eye when RBP4-bound ROL is the only transport pathway in the fasting condition or under vitamin A deficiency conditions.<\/jats:p>","DOI":"10.3390\/nu14122371","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"2371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mice Lacking the Systemic Vitamin A Receptor RBPR2 Show Decreased Ocular Retinoids and Loss of Visual Function"],"prefix":"10.3390","volume":"14","author":[{"given":"Rakesh","family":"Radhakrishnan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-9494","authenticated-orcid":false,"given":"Heidi","family":"Roehrich","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Walterhouse","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A.","family":"Kondkar","sequence":"additional","affiliation":[{"name":"Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Fitzgibbon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-2923","authenticated-orcid":false,"given":"Manas R.","family":"Biswal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn P.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA"},{"name":"Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1074\/jbc.R111.303990","article-title":"Metabolism of carotenoids and retinoids related to vision","volume":"287","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bbalip.2011.06.010","article-title":"Membrane Receptors and Transporters Involved in the Function and Transport of Vitamin A and its Derivatives","volume":"1821","author":"Sun","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"32198","DOI":"10.1074\/jbc.M111.253070","article-title":"Uptake of dietary retinoids at the maternal-fetal barrier: In vivo evidence for the role of lipoprotein lipase and alternative pathways","volume":"286","author":"Wassef","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/nu3010063","article-title":"Vitamin A metabolism. An update","volume":"3","author":"Clugston","year":"2011","journal-title":"Nutrients"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Borel, P., and Desmarchelier, C. (2017). Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability. Nutrients, 9.","DOI":"10.3390\/nu9030246"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1093\/ajcn\/69.5.931","article-title":"Biochemical but not clinical vitamin A deficiency results from mutations in the gene for retinol binding protein","volume":"69","author":"Biesalski","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1093\/emboj\/18.17.4633","article-title":"Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein","volume":"18","author":"Quadro","year":"1999","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbalip.2011.06.002","article-title":"Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids","volume":"1821","author":"Harrison","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bbalip.2011.04.010","article-title":"Mammalian carotenoid-oxygenases: Key players for carotenoid function and homeostasis","volume":"1821","author":"Lobo","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1126\/science.1136244","article-title":"Membrane receptor for retinol binding protein mediates cellular uptake of vitamin A","volume":"315","author":"Kawaguchi","year":"2007","journal-title":"Science"},{"key":"ref_11","first-page":"229","article-title":"STRA6: Role in cellular retinol uptake and efflux","volume":"4","author":"Kelly","year":"2015","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5402","DOI":"10.1093\/hmg\/ddu258","article-title":"STRA6 is critical for cellular vitamin A uptake and homeostasis","volume":"23","author":"Amengual","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1074\/jbc.M112.369132","article-title":"Liver retinol transporter and receptor for serum retinol-binding protein (RBP4)","volume":"288","author":"Alapatt","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16207","DOI":"10.1038\/s41598-017-16498-9","article-title":"The Retinol Binding Protein Receptor 2 (Rbpr2) is required for Photoreceptor Outer Segment Morphogenesis and Visual Function in Zebrafish","volume":"7","author":"Shi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24528","DOI":"10.1074\/jbc.M113.484014","article-title":"The STRA6 receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining vitamin A homeostasis in tissues other than the eye","volume":"23","author":"Berry","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/978-3-319-75402-4_69","article-title":"The Retinol-Binding Protein Receptor 2 (Rbpr2) Is Required for Photoreceptor Survival and Visual Function in the Zebrafish","volume":"1074","author":"Lobo","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1177\/0883073809333541","article-title":"Permanent visual loss due to dietary vitamin A deficiency in an autistic adolescent","volume":"24","author":"McAbee","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.exer.2009.04.012","article-title":"Retinoic acid signaling in mammalian eye development","volume":"89","author":"Cvekl","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1167\/iovs.05-0820","article-title":"Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: A potential therapy for treatment of lipofuscin-based retinal diseases","volume":"46","author":"Radu","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1167\/iovs.07-1470","article-title":"Accelerated accumulation of lipofuscin pigments in the RPE of a mouse model for ABCA4-mediated retinal dystrophies following Vitamin A supplementation","volume":"49","author":"Radu","year":"2008","journal-title":"Investig. Ophtalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/13816810.2018.1488174","article-title":"Vitamin A in Stargardt disease-an evidence-based update","volume":"39","author":"Federspiel","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1124\/mol.118.112581","article-title":"Protective Effect of a Locked Retinal Chromophore Analog against Light-Induced Retinal Degeneration","volume":"94","author":"Gao","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8415","DOI":"10.1073\/pnas.1506960112","article-title":"Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization","volume":"112","author":"Barnard","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1167\/iovs.15-18993","article-title":"Acute Stress Responses Are Early Molecular Events of Retinal Degeneration in Abca4-\/-Rdh8-\/- Mice After Light Exposure","volume":"57","author":"Parmar","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1167\/iovs.09-3944","article-title":"Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina","volume":"50","author":"Maeda","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1167\/iovs.09-3581","article-title":"Evaluation of potential therapies for a mouse model of human age-related macular degeneration caused by delayed all-trans- retinal clearance","volume":"50","author":"Maeda","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15173","DOI":"10.1074\/jbc.M900322200","article-title":"Involvement of all-trans-retinal in acute light-induced retinopathy of mice","volume":"284","author":"Maeda","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26684","DOI":"10.1074\/jbc.M804505200","article-title":"Retinopathy in mice induced by disrupted all-trans- retinal clearance","volume":"283","author":"Maeda","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1080\/14712598.2018.1513486","article-title":"Stargardt macular dystrophy and evolving therapies","volume":"18","author":"Hussain","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11574","DOI":"10.1074\/jbc.RA118.002062","article-title":"A non- retinoid antagonist of retinol-binding protein 4 rescues phenotype in a model of Stargardt disease without inhibiting the visual cycle","volume":"293","author":"Racz","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6904","DOI":"10.1073\/pnas.1524774113","article-title":"Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration","volume":"113","author":"Ueda","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1073\/pnas.1600474113","article-title":"Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics","volume":"113","author":"Sparrow","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100215","DOI":"10.1016\/j.jlr.2022.100215","article-title":"Genetic dissection in mice reveals a dynamic crosstalk between the delivery pathways of vitamin A","volume":"6","author":"Moon","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ydbio.2008.09.030","article-title":"The temporal requirement for vitamin A in the developing eye: Mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina","volume":"325","author":"See","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.cell.2011.11.034","article-title":"SnapShot: Retinoic acid signaling","volume":"147","author":"Kumar","year":"2011","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1093\/hmg\/ddt179","article-title":"ALDH1A3 loss of function causes bilateral anophthalmia\/microphthalmia and hypoplasia of the optic nerve and optic chiasm","volume":"22","author":"Yahyavi","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.3390\/nu4122069","article-title":"Retina, retinol, retinal and the natural history of vitamin A as a light sensor","volume":"19","author":"Zhong","year":"2012","journal-title":"Nutrients"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.2218545","article-title":"Transport and storage of vitamin A","volume":"250","author":"Blomhoff","year":"1990","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3390\/membranes5030425","article-title":"Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6","volume":"5","author":"Kawaguchi","year":"2015","journal-title":"Membranes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10581","DOI":"10.1073\/pnas.162182899","article-title":"A class B scavenger receptor mediates the cellular uptake of carotenoids in Drosophila","volume":"99","author":"Kiefer","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1096\/fj.09-150995","article-title":"ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production","volume":"24","author":"Lobo","year":"2010","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9017","DOI":"10.1074\/jbc.M112.444240","article-title":"Genetics and diet regulate vitamin A production via the homeobox transcription factor ISX","volume":"288","author":"Lobo","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1093\/hmg\/ddv072","article-title":"A diet responsive regulatory network controls intestinal fat-soluble vitamin and carotenoid absorption","volume":"24","author":"Lobo","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1074\/jbc.M608315200","article-title":"Topology and membrane association of lecithin: Retinol acyltransferase","volume":"19","author":"Moise","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cmet.2008.01.009","article-title":"RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome","volume":"7","author":"Isken","year":"2008","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1074\/jbc.M609109200","article-title":"Sequestration of retinyl esters is essential for retinod signaling in the zebrafish embryos","volume":"282","author":"Isken","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"24216","DOI":"10.1074\/jbc.M112.353979","article-title":"Lecithin:retinol acyltransferase is critical for cellular uptake of vitamin A from serum retinol-binding protein","volume":"287","author":"Amengual","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40226","DOI":"10.1074\/jbc.M509643200","article-title":"Disruption of the lecithin:retinol acyltransferase gene makes mice more susceptible to vitamin A deficiency","volume":"280","author":"Liu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/nu8110676","article-title":"Molecular Basis for Vitamin A Uptake and Storage in Vertebrates","volume":"8","author":"Chelstowska","year":"2016","journal-title":"Nutrients"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1242\/dev.00437","article-title":"Provitamin A conversion to retinal via the beta, beta-carotene-15,15\u2019-oxygenase (bcox) is essential for pattern formation and differentiation during zebrafish embryogenesis","volume":"130","author":"Lampert","year":"2003","journal-title":"Development"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1460-9568.2004.03830.x","article-title":"Photoreceptor morphology is severely affected in the beta,beta-carotene-15,15\u2019-oxygenase (bcox) zebrafish morphant","volume":"21","author":"Biehlmaier","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0083-6729(06)75005-1","article-title":"Conversion of beta-carotene to retinal pigment","volume":"75","author":"Biesalski","year":"2007","journal-title":"Vitam. Horm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1021\/bi8002082","article-title":"Mapping the membrane topology and extracellular ligand binding domains of the retinol binding protein receptor","volume":"47","author":"Kawaguchi","year":"2008","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15160","DOI":"10.1074\/jbc.M801060200","article-title":"An essential ligand-binding domain in the membrane receptor for retinol-binding protein revealed by large-scale mutagenesis and a human polymorphism","volume":"30","author":"Kawaguchi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.cell.2015.03.006","article-title":"Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Eye Disease","volume":"161","author":"Chou","year":"2015","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00232-012-9463-1","article-title":"STRA6-catalyzed vitamin A influx, efflux, and exchange","volume":"245","author":"Kawaguchi","year":"2012","journal-title":"J. Membr. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/978-1-60327-325-1_20","article-title":"Techniques to study specific cell-surface receptor-mediated cellular Vitamin A uptake","volume":"652","author":"Kawaguchi","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1126\/science.aad8266","article-title":"Structure of the STRA6 receptor for retinol uptake","volume":"353","author":"Chen","year":"2016","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1167\/iovs.12-9662","article-title":"The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL\/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes","volume":"53","author":"Mattapallil","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1167\/iovs.11-8476","article-title":"Retinoid content, visual responses, and ocular morphology are compromised in the retinas of mice lacking the retinol-binding protein receptor, STRA6","volume":"53","author":"Ruiz","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Terra, R., Wang, X., Hu, Y., Charpentier, T., Lamarre, A., Zhong, M., Sun, H., Mao, J., Qi, S., and Luo, H. (2013). To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082808"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1101\/SQB.1997.062.01.021","article-title":"Analysis of Fgf8 gene function in vertebrate development","volume":"62","author":"Lewandoski","year":"1997","journal-title":"Cold Spring Harb. Symp. Quant. Bol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14814","DOI":"10.1074\/jbc.M117.795674","article-title":"The exocyst is required for photoreceptor ciliogenesis and retinal development","volume":"292","author":"Lobo","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Solanki, A.K., Biswal, M.R., Walterhouse, S., Martin, R., Kondkar, A.A., Kn\u00f6lker, H.-J., Rahman, B., Arif, E., Husain, S., and Montezuma, S.R. (2021). Loss of Motor Protein MYO1C Causes Rhodopsin Mislocalization and Results in Impaired Visual Function. Cells, 10.","DOI":"10.3390\/cells10061322"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lobo, G.P., Au, A., Kiser, P.D., and Hagstrom, S.A. (2017). Involvement of Endoplasmic Reticulum Stress in TULP1 Induced Retinal Degeneration. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0151806"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1096\/fj.10-173906","article-title":"A mitochondrial enzyme degrades carotenoids and protects against oxidative stress","volume":"25","author":"Amengual","year":"2011","journal-title":"FASEB J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1242\/dev.079632","article-title":"BCDO2 acts as a carotenoid scavenger and gatekeeper for the mitochondrial apoptotic pathway","volume":"139","author":"Lobo","year":"2012","journal-title":"Development"},{"key":"ref_68","first-page":"3","article-title":"Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis","volume":"40","author":"Seeliger","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Steinhoff, J.S., Lass, A., and Schupp, M. (2022). Nutrients. Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease. Nutrients, 14.","DOI":"10.3390\/nu14061236"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"659977","DOI":"10.3389\/fphys.2021.659977","article-title":"Biological Functions of RBP4 and Its Relevance for Human Diseases","volume":"12","author":"Steinhoff","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Solanki, A.K., Kondkar, A.A., Fogerty, J., Su, Y., Kim, S.H., Lipschutz, J.H., Nihalani, D., Perkins, B.D., and Lobo, G.P. (2020). A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish. Cells, 9.","DOI":"10.20944\/preprints202003.0296.v1"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1074\/jbc.M114.613968","article-title":"An alternative retinoic acid-responsive Stra6 promoter regulated in response to retinol deficiency","volume":"290","author":"Laursen","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1194\/jlr.R030833","article-title":"Vitamin A and retinoid signaling: Genomic and nongenomic effects","volume":"54","author":"Piskunov","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Martin Ask, N., Leung, M., Radhakrishnan, R., and Lobo, G.P. (2021). Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for Dietary Vitamin A Uptake, Storage, and Transport to the Eye. Nutrients, 13.","DOI":"10.3390\/nu13113987"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ng1246","article-title":"Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis","volume":"35","author":"Woodruff","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/hmg\/ddab267","article-title":"The vitamin A transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling","volume":"31","author":"Ramkumar","year":"2022","journal-title":"Hum. Mol. Genet."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:25:52Z","timestamp":1760138752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["nu14122371"],"URL":"https:\/\/doi.org\/10.3390\/nu14122371","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]}}}