Editing Retinol (section)

==Biological roles==
Retinol or other forms of vitamin A are needed for eyesight, maintenance of the skin, and human development.<ref name=drugs/> Other than for vision, which requires 11-cis retinal, the active compound is retinoic acid, synthesized from retinal, in turn synthesized from retinol. The differing biological roles of retinoic acid depend on its [[stereochemistry]] and whether it is present in the all-trans, 9-cis, or 13-cis forms.<ref>{{cite journal | vauthors = Esposito M, Amory JK, Kang Y | title = The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes | journal = The Journal of Experimental Medicine | volume = 221 | issue = 9 | date = September 2024 | pmid = 39133222 | doi = 10.1084/jem.20240519 | doi-access = free | pmc = 11318670 }}</ref>

===Embryology===
Retinoic acid via the retinoic acid receptor influences the process of cell differentiation and, hence, the growth and development of embryos. During development, there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond to retinoic acid differently depending on the amount present. For example, in vertebrates, the hindbrain transiently forms eight [[rhombomeres]] and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead, rhombomeres 1–4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Homeobox (Hox) genes that encode different homeodomain transcription factors which in turn can turn on cell type-specific genes.<ref name=gd>{{cite journal | vauthors = Duester G | title = Retinoic acid synthesis and signaling during early organogenesis | journal = Cell | volume = 134 | issue = 6 | pages = 921–931 | date = September 2008 | pmid = 18805086 | pmc = 2632951 | doi = 10.1016/j.cell.2008.09.002 }}</ref> Deletion of the Homeobox (Hox-1) gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2.  Retinoic acid is not required for patterning of the retina as originally proposed, but retinoic acid synthesized in the retina is secreted into the surrounding [[mesenchyme]] where it is required to prevent overgrowth of perioptic mesenchyme which can cause microphthalmia, defects in the cornea and eyelid, and rotation of the optic cup.<ref name="Duester_2008"/>

===Stem cell biology===
Synthetic retinoic acid is used in [[Cellular differentiation|differentiation]] of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways. It is thought to initiate differentiation into several different cell lineages through activation of the [[Retinoic acid receptor]]. It has numerous applications in the experimental induction of stem cell differentiation; amongst these is the differentiation of human [[embryonic stem cell]]s to posterior foregut lineages.<ref name=gd/>

===Vision===
{{Main|Visual cycle}}
Retinol is an essential compound in the cycle of light-activated chemical reactions called the "[[visual cycle]]" that underlies vertebrate vision. Retinol is converted by the protein [[RPE65]] within the [[pigment epithelium]] of the [[retina]] into 11-''cis''-retinal. This molecule is then transported into the [[retina]]'s [[photoreceptor cell]]s (the [[rod cell|rod]] or [[cone cell|cone]] cells in mammals) where it binds to an [[opsin]] protein and acts as a light-activated molecular switch.  When 11-''cis''-retinal absorbs light it [[cis-trans isomerism|isomerizes]] into all-''trans''-retinal. The change in the shape of the molecule in turn changes the configuration of the opsin in a cascade that leads to the [[Action potential|neuronal firing]], which signals the detection of light.<ref>{{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM |date=2001 | chapter = Phototransduction |chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK10806/ |title = Neuroscience |publisher=Sinauer Associates | edition = 2nd }}</ref> The opsin then splits into the protein component (such [[metarhodopsin]]) and the cofactor all-''trans''-retinal. The regeneration of active opsin requires conversion of all-''trans''-retinal back to 11-''cis''-retinal via retinol. The regeneration of 11-''cis''-retinal occurs in vertebrates via the conversion of all-''trans''-retinol to 11-''cis''-retinol in a sequence of chemical transformations that occurs primarily in the pigment epithelial cells.<ref name=bs>{{cite journal | vauthors = Sahu B, Maeda A | title = Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function | journal = Nutrients | volume = 8 | issue = 11 | pages = 746 | date = November 2016 | pmid = 27879662 | pmc = 5133129 | doi = 10.3390/nu8110746 | doi-access = free }}</ref>

Without adequate amounts of retinol, regeneration of rhodopsin is incomplete and [[night blindness]] occurs. Night blindness, the inability to see well in dim light, is associated with a deficiency of [[vitamin A]], a class of compounds that includes retinol and retinal. In the early stages of [[vitamin A]] deficiency, the more light-sensitive and abundant [[rod cell|rod]]s, which have [[rhodopsin]], have impaired sensitivity, and the [[cone cell]]s are less affected. The cones are less abundant than rods and come in three types, each contains its own type of [[iodopsin]], the opsins of the cones. The cones mediate [[color vision]], and vision in bright light (day vision).

===Glycoprotein synthesis===
[[Glycoprotein]] synthesis requires adequate vitamin A status. In severe vitamin A deficiency, lack of glycoproteins may lead to [[corneal ulcer]]s or liquefaction.<ref>{{cite book | vauthors = Starck T |title=Advances in Corneal Research |chapter=Severe Corneal Ulcerations and Vitamin A Deficiency |publisher=Springer, Boston, MA |year=1997 |page=558 |isbn=978-1-4613-7460-2 |doi=10.1007/978-1-4615-5389-2_46 }}</ref>

===Immune system===
Vitamin A is involved in maintaining a number of immune cell types from both the innate and acquired immune systems.<ref>{{cite web|url=https://www.sciencedaily.com/releases/2015/07/150709132634.htm|title=Vitamin A directs immune cells to intestines|website=ScienceDaily|language=en|access-date=17 March 2020}}</ref> These include the [[lymphocytes]] ([[B-cells]], [[T-cells]], and [[natural killer cells]]), as well as many myelocytes ([[neutrophils]], [[macrophages]], and myeloid [[dendritic cells]]). Vitamin A maintains immune barriers in the gut through its activity as retinoic acid.<ref>{{cite journal | vauthors = Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H | title = Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid | journal = Science | volume = 317 | issue = 5835 | pages = 256–260 | date = July 2007 | pmid = 17569825 | doi = 10.1126/science.1145697 }}</ref>

===Skin===
Deficiencies in vitamin A have been linked to an increased susceptibility to skin infection and inflammation.<ref name="Roche2021">{{cite journal | vauthors = Roche FC, Harris-Tryon TA | title = Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review | journal = Nutrients | volume = 13 | issue = 2 | page = 302 | date = January 2021 | pmid = 33494277 | pmc = 7909803 | doi = 10.3390/nu13020302 | doi-access = free }}</ref> Vitamin A appears to modulate the [[innate immune response]] and maintains homeostasis of [[epithelial tissues]] and mucosa through its metabolite, retinoic acid (RA). As part of the innate immune system, [[toll-like receptors]] in skin cells respond to pathogens and cell damage by inducing a pro-inflammatory immune response which includes increased RA production.<ref name="Roche2021"/> The epithelium of the skin encounters bacteria, fungi and viruses. Keratinocytes of the epidermal layer of the skin produce and secrete [[antimicrobial peptides]] (AMPs). Production of AMPs [[resistin]] and [[cathelicidin]], are promoted by RA.<ref name="Roche2021"/> Another way that vitamin A helps maintain a healthy skin and hair follicle [[microbiome]], especially on the face, is by reduction of [[sebum]] secretion, which is a nutrient source for bacteria.<ref name="Roche2021"/> Retinol has been the subject of clinical studies related to its ability to reduce the appearance of fine lines on the face and neck.<ref name="Kong 2015" /><ref>{{cite web |date=7 November 2016 |title=Vitamin A and Skin Health |url=https://lpi.oregonstate.edu/mic/health-disease/skin-health/vitamin-A |access-date=10 August 2023 |website=Linus Pauling Institute |language=en}}</ref>

===Red blood cells===
Vitamin A may be needed for normal [[haematopoiesis|red blood cell formation]];<ref>{{cite journal | vauthors = Oren T, Sher JA, Evans T | title = Hematopoiesis and retinoids: development and disease | journal = Leukemia & Lymphoma | volume = 44 | issue = 11 | pages = 1881–1891 | date = November 2003 | pmid = 14738139 | doi = 10.1080/1042819031000116661 | s2cid = 11348076 }}</ref><ref>{{cite journal | vauthors = Evans T | title = Regulation of hematopoiesis by retinoid signaling | journal = Experimental Hematology | volume = 33 | issue = 9 | pages = 1055–1061 | date = September 2005 | pmid = 16140154 | doi = 10.1016/j.exphem.2005.06.007 | doi-access = free }}</ref> deficiency causes abnormalities in [[iron metabolism]].<ref>{{cite journal | vauthors = García-Casal MN, Layrisse M, Solano L, Barón MA, Arguello F, Llovera D, Ramírez J, Leets I, Tropper E | title = Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans | journal = The Journal of Nutrition | volume = 128 | issue = 3 | pages = 646–650 | date = March 1998 | pmid = 9482776 | doi = 10.1093/jn/128.3.646 | doi-access = free }}</ref> Vitamin A is needed to produce the red blood cells from stem cells through retinoid differentiation.<ref>{{cite web|url=https://www.ebi.ac.uk/interpro/potm/2005_6/Page2.htm|title=Carotenoid Oxygenase |website=InterPro|access-date=7 November 2018}}</ref>