Editing Vitamin A (section)

===Vision and eye health===
Vitamin A status involves eye health via two separate functions. Retinal is an essential factor in [[rod cell]]s and [[cone cell]]s in the retina responding to light exposure by sending nerve signals to the brain. An early sign of vitamin A deficiency is night blindness.<ref name=PKIN2020VitA/> Vitamin A in the form of retinoic acid is essential to normal epithelial cell functions. Severe vitamin A deficiency, common in infants and young children in southeast Asia causes [[xerophthalmia]] characterized by dryness of the conjunctival epithelium and cornea. Untreated, xerophthalmia progresses to corneal ulceration and blindness.<ref name="Whitcher2001"/>

====Vision====
{{Main|visual cycle}}
The role of vitamin A in the visual cycle is specifically related to the retinal compound. Retinol is converted by the enzyme [[RPE65]] within the retinal pigment epithelium into 11-''cis''-retinal. Within the eye, 11-''cis''-retinal is bound to the protein [[opsin]] to form [[rhodopsin]] in rod cells and [[iodopsin]] in cone cells. As light enters the eye, the 11-''cis''-retinal is isomerized to the ''all-trans'' form. The ''all-trans''-retinal dissociates from the opsin in a series of steps called photo-bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. After separating from opsin, the ''all-trans''-retinal is recycled and converted back to the 11-''cis''-retinal form by a series of enzymatic reactions, which then completes the cycle by binding to opsin to reform rhodopsin in the retina.<ref name=PKIN2020VitA/> In addition, some of the ''all-trans''-retinal may be converted to ''all-trans''-retinol form and then transported with an interphotoreceptor retinol-binding protein to the retinal pigmented epithelial cells. Further esterification into ''all-trans''-retinyl esters allow for storage of ''all-trans''-retinol within the pigment epithelial cells to be reused when needed. It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin, and will lead to one of the first symptoms, night blindness.<ref name=PKIN2020VitA/><ref name="Combs2008">{{cite book |title=The Vitamins: Fundamental Aspects in Nutrition and Health | vauthors = Combs GF |year=2008 |edition=3rd |publisher=Elsevier Academic Press |location=Burlington, MA |isbn=978-0-12-183493-7}}</ref><ref name="Miller"/>

====Night blindness====
{{Main|Nyctalopia}}
Vitamin A deficiency-caused [[Nyctalopia|night blindness]] is a reversible difficulty for the eyes to adjust to dim light. It is common in young children who have a diet inadequate in retinol and β-carotene. A process called [[Adaptation (eye)|dark adaptation]] typically causes an increase in photopigment amounts in response to low levels of illumination. This increases light sensitivity by up to 100,000 times compared to normal daylight conditions. Significant improvement in night vision takes place within ten minutes, but the process can take up to two hours to reach maximal effect.<ref name="Wolf2001"/> People expecting to work in a dark environment wore red-tinted goggles or were in a red light environment to not reverse the adaptation because red light does not deplete rhodopsin versus what occurs with yellow or green light.<ref name="Miller">{{cite journal |url=https://apps.dtic.mil/sti/citations/ADA257059 |archive-url=https://web.archive.org/web/20220104192142/https://apps.dtic.mil/sti/citations/ADA257059 |url-status=live |archive-date=4 January 2022 |title=Night Vision Manual for the Flight Surgeon|vauthors=Miller RE, Tredici TJ |date=1 August 1992 |website=US Department of Defense, Defense Technical Information Center |access-date=4 January 2022}}</ref>

====Xerophthalmia and childhood blindness====
{{Main|Xerophthalmia}}
[[File:Typical location of Bitot's spots.jpg|thumb|Typical location of Bitot's spots]]
Xerophthalmia, caused by a severe vitamin A deficiency, is described by pathologic dryness of the conjunctival epithelium and cornea. The conjunctiva becomes dry, thick, and wrinkled. Indicative is the appearance of Bitot's spots, which are clumps of keratin debris that build up inside the conjunctiva. If untreated, xerophthalmia can lead to dry eye syndrome, [[corneal ulceration]] and ultimately to blindness as a result of cornea and retina damage. Although xerophthalmia is an eye-related issue, prevention (and reversal) are functions of retinoic acid having been synthesized from retinal rather than the 11-''cis''-retinal to rhodopsin cycle.<ref name="Akhtar2013"/>

Throughout southeast Asia, estimates are that more than half of children under the age of six years have subclinical vitamin A deficiency and night blindness, with progression to xerophthalmia being the leading cause of preventable childhood blindness.<ref name="Akhtar2013">{{cite journal | vauthors = Akhtar S, Ahmed A, Randhawa MA, Atukorala S, Arlappa N, Ismail T, Ali Z | title = Prevalence of vitamin A deficiency in South Asia: causes, outcomes, and possible remedies | journal = Journal of Health, Population, and Nutrition | volume = 31 | issue = 4 | pages = 413–423 | date = December 2013 | pmid = 24592582 | pmc = 3905635 | doi = 10.3329/jhpn.v31i4.19975 }}</ref> Estimates are that each year there are 350,000 cases of childhood blindness due to vitamin A deficiency.<ref name="Whitcher2001">{{cite journal | vauthors = Whitcher JP, Srinivasan M, Upadhyay MP | title = Corneal blindness: a global perspective | journal = Bulletin of the World Health Organization | volume = 79 | issue = 3 | pages = 214–221 | date = 2001 | pmid = 11285665 | pmc = 2566379 | doi = }}</ref> The causes are vitamin A deficiency during pregnancy, followed by low transfer of vitamin A during lactation and infant/child diets low in vitamin A or β-carotene.<ref name="Akhtar2013"/><ref name="Whitcher2001"/> The [[prevalence]] of pre-school age children who are blind due to vitamin A deficiency is lower than expected from [[Incidence (epidemiology)|incidence of new cases]] only because childhood vitamin A deficiency significantly increases all-cause mortality.<ref name="Whitcher2001"/>

According to a 2017 Cochrane review, vitamin A deficiency, using serum retinol less than 0.70&nbsp;μmol/L as a criterion, is a major public health problem affecting an estimated 190 million children under five years of age in low- and middle-income countries, primarily in Sub-Saharan Africa and Southeast Asia. In lieu of or in combination with food fortification programs, many countries have implemented public health programs in which children are periodically given very large oral doses of synthetic vitamin A, usually retinyl palmitate, as a means of preventing and treating vitamin A deficiency. Doses were 50,000 to 100,000 IU ([[International unit]]s) for children aged 6 to 11 months and 100,000 to 200,000 IU for children aged 12 months to five years, the latter typically every four to six months. In addition to a 24% reduction in all-cause mortality, eye-related results were reported. Prevalence of Bitot's spots at follow-up were reduced by 58%, night blindness by 68%, xerophthalmia by 69%.<ref name="Imdad2017"/>