Vitamin a transporters in visual function: A mini review on membrane receptors for dietary vitamin a uptake, storage, and transport to the eye

Nicasio Martin Ask, Matthias Leung, Rakesh Radhakrishnan, Glenn P. Lobo

Research output: Contribution to journalReview articlepeer-review

Abstract

Vitamins are essential compounds obtained through diet that are necessary for normal development and function in an organism. One of the most important vitamins for human physiology is vitamin A, a group of retinoid compounds and carotenoids, which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in the vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids such as β-carotene from plants or preformed vitamin A such as retinyl esters from animal sources are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carotenoid cleavage oxygenases (CCOs), such as Beta-carotene 15,15’-monooxygenase (BCO1), to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein 4 receptor 2 (RBPR2) in systemic tissues (e.g., in the retina and the liver, respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature regarding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

Original languageEnglish (US)
Article number3987
JournalNutrients
Volume13
Issue number11
DOIs
StatePublished - Nov 2021

Bibliographical note

Funding Information:
Author Contributions: Conceptualization, G.P.L. and R.R.; methodology, G.P.L.; software, R.R.; validation, N.M.A., M.L., R.R. and G.P.L.; formal analysis, R.R. and G.P.L.; investigation, G.P.L., N.M.A., R.R. and M.L.; resources, G.P.L.; data curation, G.P.L. and R.R.; writing—original draft preparation, G.P.L., N.M.A. and M.L.; writing—review and editing, G.P.L., N.M.A. and M.L.; visualization, G.P.L. and R.R.; supervision, G.P.L. and R.R.; project administration, G.P.L.; funding ac-qaundisiRti.oRn.;, sGu.pPe.Lrv. iAsilol na,uGth.Po.rLs. haanvdeR re.Ra.d; parnodje acgt raedemd itnoi stthreatpiounb,liGsh.Pe.Ld. ;vfeurnsidoinn gofa tchqeu misiatinouns,cGri.pPt.L. . All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by the National Institute of Health-National Eye Institute (NIH-NFuEnI)dginragn: tsT Rhi2s1EwYo0r2k50w3a4s asnudp Rp0o1rEteYd03b0y88th9 etoNGa.tPio.Ln.a l Institute of Health-National Eye Institute (NIH-NEI) grants R21EY025034 and R01EY030889 to G.P.L. Institutional Review Board Statement: Not applicable. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Data Availability Statement: Not applicable.

Publisher Copyright:
© 2021 by the authorsLicensee MDPI, Basel, Switzerland.

Keywords

  • All-trans retinol
  • LRAT
  • Photoreceptors
  • RBP4
  • RBPR2
  • Retinol-binding proteins
  • Retinyl esters
  • STRA6
  • Visual function
  • Vitamin A transporters

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