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Vitamin A and the eye: An old tale for modern times


Abstract and Figures

Clinical presentations associated with vitamin A deficiency persist in poor regions globally with the same clinical features as those described centuries ago. However, new forms of vitamin A deficiency affecting the eyes, which have become widespread, as a result of modern societal habits are of increasing concern. Ophthalmic conditions related to vitamin A deficiency require the combined attention of ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due to their potential severity and the diversity of causes. As the eyes and their adnexa are particularly sensitive to vitamin A deficiency and excess, ocular disturbances are often early indicators of vitamin A imbalance. The present review describes the clinical manifestations of hypovitaminosis A with an emphasis on so-called modern dietary disorders and multidisciplinary treatment approaches. The present review also discusses the relationship between retinoic acid therapy and dry eye disease.
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56 
Night blindness, xerophthalmia, Bitot’s spot, keratitis, and kera-
tomalacia are well-known clinical manifestations of hypovitaminosis
A(1). However, this condition is classically related to food deprivation
associated with malabsorption syndrome resulting from poverty
and/or chronic disease(1-3).
The present review aims to inform health professionals of the
modern presentations, causes, associated systemic diseases, and risk
factors of hypovitaminosis A. The utility of retinoic acid application
for the treatment of skin diseases and dry eye is also discussed(4).
Herein, we present the clinical presentation of hypovitaminosis A
and discuss strategies for the investigation and treatment of the
causes and consequences of hypovitaminosis A and side effects of
the use of retinoic acid (a form of vitamin A) in dermatological and
oncological therapies.
The classical clinical presentation of the disease currently known
as vitamin A deficiency was first described in antique medical docu-
ments of the ancient Egyptian civilization, although underlying me-
Clinical presentations associated with vitamin A deficiency persist in poor regions
globally with the same clinical features as those described centuries ago. However,
new forms of vitamin A deficiency affecting the eyes, which have become wides-
pread, as a result of modern societal habits are of increasing concern. Ophthalmic
conditions related to vitamin A deficiency require the combined attention of
ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due
to their potential severity and the diversity of causes. As the eyes and their adnexa
are particularly sensitive to vitamin A deficiency and excess, ocular disturbances
are often early indicators of vitamin A imbalance. The present review describes the
clinical manifestations of hypovitaminosis A with an emphasis on so-called modern
dietary disorders and multidisciplinary treatment approaches. The present review
also discusses the relationship between retinoic acid therapy and dry eye disease.
Keywords: Vitamin A deficiency/complications; Eye manifestations; Bariatric surgery;
Blepharoplasty; Refractive surgical procedures; Xerophthalmia
As apresentações clínicas associadas à deficiência de vitamina A persistem em regiões
pobres ao redor do mundo com os mesmos achados clínicos descritos há séculos.
No entanto, novas formas de problemas causados pela vitamina A afetam os olhos,
estão associados com os hábitos da sociedade moderna e tem causado preocupação.
Eles exigem a atenção dos oftalmologistas, pediatras, internistas, dermatologistas e
nutricionistas, devido à sua gravidade e diversidade de causas. Uma vez que os olhos
e seus anexos são órgãos muito sensíveis à deficiência e excesso de vitamina A, mani-
festações oculares podem ser indicadores precoces do desequilíbrio de vitamina A. Essa
revisão traz as manifestações clínicas de hipovitaminose A enfatizando os chamados
distúrbios dietéticos modernos e formas de abordagem multidisciplinar. E também traz
evidências sobre a relação entre a terapia com ácido retinóico e doença do olho seco.
Descritores: Deficiência de vitamina A/complicações; Manifestações oculares; Cirurgia
bariátrica; Blefaroplastia; Procedimentos cirúrgicos refrativos; Xeroftalmia
chanisms were elucidated more recently. The causes of deficiencies
in the micronutrient vitamin A, the biochemical vitamin A pathway,
food sources of retinol (vitamin A) and its metabolites, and the phy-
siological roles of vitamin A have only begun to be understood since
the 20th century(5-9) (Figure 1; Table 1).
Interestingly, one of the most complete and objective des-
criptions of the clinical manifestations of hypovitaminosis A was
published decades before the specific underlying cause was known
by the Brazilian ophthalmologist, Manoel da Gama Lobo, in 1865(10).
Dr. Gama Lobo reported four cases of children, all descendants of
slaves, with ocular disease who subsequently developed lung and
digestive disorders before ultimately dying. In this report, the disea-
se was termed Ophthalmia Braziliana, and the clinical progression
was comprehensively detailed. Food deprivation was identified
and credited to the practice of extensive monoculture in the farms
of Southeast Brazil, in that century dedicated to the production of
coffee and sugar.
Dr. Gama Lobo attributed the signs and symptoms observed
in his patients to the poor diet of slaves and their descendants, a
problem that he never saw in his homeland to north of the country
Vitamin A and the eye: an old tale for modern times
A vitamina A e o olho: uma velha história em tempos modernos
Jacqueline Ferreira Faustino1, alFredo ribeiro-silva2, rodrigo Faeda dalto1, Marcelo Martins de souza1, João Marcello Fortes Furtado1,
guteMberg de Melo rocha3, Monica alves4, eduardo Melani rocha1
Submitted for publication: September 8, 2015
Accepted for publication: October 20, 2015
1 Departamento de Oftalmologia, Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Faculdade de
Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
2 Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade
de São Paulo, Ribeirão Preto, SP, Brazil.
3 Depar tamento de Medicina Social, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, Ribeirão Preto, SP, Brazil.
4 Departamento de Oftalmologia e Otorrinolaringologia da Faculdade de Ciências Médicas, Univer-
sidade Estadual de Campinas, Campinas, SP, Brazil.
Funding: This study was supported by CAPES, CNPq, FAPESP, FAEPA, and NAP-FTO-USP.
Disclosure of potential conflicts of interest: None of the authors have any potential conflicts of
interest to disclose.
Corresponding author: Eduardo Melani Rocha. Department of Ophthalmology, Otorhinolaryngology
and Head & Neck Surgery, School of Medicine at Ribeirao Preto, University of Sao Paulo. Av.
Bandeirantes, 3.900 - Ribeirão Preto, SP - 14049-900 - Brazil - E-mail:
where agriculture production was dedicated to local consumption
and therefore more variable and abundant. At the end of his report,
Dr. Gama Lobo called the attention of legislators to the need for
laws aimed at preventing the sequence of problems he outlined. His
paper was published in Portuguese and in German but is relatively
unknown to the majority of the medical community, although it is
now freely available online(11,12).
Recent epidemiologic data from Brazil in a study population of
3,499 children aged between 6 and 59 months and 5,698 women
aged between 15 and 49 years revealed that hypovitaminosis A is
present in all five regions of Brazil with a prevalence of 17.4% and
12.3% among children and women, respectively(13). The highest
prevalence was found to be in urban areas and the northeastern and
southeastern regions of the country.
ClAssIC DIseAse
The typical medical scenarios leading to hypovitaminosis A are
low food intake, intestinal parasitosis, malabsorption syndromes, and
diets containing low amounts of vitamin A (Figure 2).
Hypovitaminosis A is classically caused by food deprivation. It is
present in rural areas and the peripheries of large cities in South Asia,
Africa, and Latin America, and the poor communities of large cities
of developed countries(14-17). The most vulnerable individuals are chil-
dren and pregnant women. The prevalence of hypovitaminosis A can
reach 50% in children under 6 years of age in certain areas(18). Labo-
ratory confirmation of the diagnosis of hypovitaminosis A is defined
as a serum retinol level <0.3 mg/l or 0.7 µM(19).
In addition to ocular problems, hypovitaminosis A also predispo-
ses individuals to retarded growth, infertility, congenital malforma-
tions, infections, and early mortality(18,20). The issue of vitamin A defi-
ciency in these populations, distributed in more than 45 countries,
has been the target of international preventive programs of vitamin
A supplementation and periodic evaluation(16,18,19).
Individuals suffering from food deprivation and malabsorption
are often infected with intestinal parasite diseases, such as Ascaris
lumbricoides and Ancilostomides, Giardia lamblia, which may aggra-
vate the inflammatory background and the signs and symptoms of
hypovitaminosis A(21-24).
Other well-known causes of vitamin A deficiency can be grouped
into conditions associated with malabsorption syndrome. The treat-
ments of several diseases that cause digestive disturbances and/or
absorption of lipids and vitamin A have improved in recent decades
leading to increased life expectancy and improved the clinical con-
trol of hypovitaminosis A allowing the majority of patients to lead
a normal life. However, the majority of these patients will develop
xerophthalmia (the specific term for hypovitaminosis A-related dry
eye), which may progress to more severe ocular damage and other
clinical manifestations of vitamin A depletion(25-27).
Acquired diseases associated with malabsorption syndrome known
to cause hypovitaminosis A include chronic pancreatitis caused by
chronic alcoholism, liver and pancreas autoimmunity, Crohn’s disease,
and ulcerative colitis, among other diseases affecting the digestive
Congenital diseases associated with malabsorption syndrome and
hypovitaminosis A include cystic fibrosis and short bowel syndrome,
among other genetic diseases that may impair intestinal vitamin A
absorption in individuals with normal or high oral intake of retinoid
and carotenoids(2,29,30).
The fourth group of conditions that classically cause hypovitami-
nosis A is those that may initially lead to malabsorption syndrome but
later progresses to impaired hepatic storage of vitamin A. Biliary cir-
rhosis, chronic hepatitis, and chronic cirrhosis caused by toxic agents,
viruses, and other causes may lead to hypovitaminosis A and should
be screened for and treated by parenteral vitamin A supplementation
according to body mass index and level of vitamin A deficiency(31).
In recent decades, the conditions known to induce hypovitami-
nosis A have been classified into four groups. Despite their varying
prevalence, such conditions should be carefully considered by
ophthalmologists during routine clinical practice.
Modern causes of hypovitaminosis A that may also lead to xe-
rophthalmia and other eye diseases and cause blindness are shown
in (Figure 2 and Table 2) and comprising voluntary ingestion of low
vitamin A diets or restrictive diets (e.g., vegetarian or cafeteria diets),
psychiatric eating disorders (e.g., anorexia and bulimia), bariatric
Figure 1. Metabolic steps underlying vitamin A deciency from the dietary level to tar-
get cells.
Table 1. Vitamin A nomenclature
Name Group Characteristics
Retinoids Vitamin A and natural or synthetic derivate Similar chemical polyenes and polar end groups
Carotenes α-Carotene, β-carotene, g-carotene, and the xanthophyll β-cryptoxanthin Β-ionine rings
Vitamin A Group of lipophilic nutritional compounds Essential and broad effects on chordate animal bodies
Provitamin A Carotenes and retinyl esters Dietary and pharmaceutical sources of vitamin A
Retinoic acid Metabolite of vitamin A Transcription factor binding to cell nuclear receptors
Retinal Form of vitamin A Essential for vision function
Retinol Form of vitamin A Growth and development functions
Tretinoin All trans retinoic acid Pharmaceutical formulas
1 IU of vitamin A = 0.3 μg retinol = 0.34 μg retinil acetate = 0.6 μg β-carotene.
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surgeries mimicking malabsorption syndrome, and chronic diseases
that affect organs involved in vitamin A digestion or clearance (e.g.,
Sjögren’s syndrome and kidney failure).
Restrictive diets resulting from dietary behaviors may lead to
a status of hypovitaminosis A and the consequences mentioned
above. Diets adopted in conjunction with drugs to reduce appetite,
diets with monotonous ingredients, and diets with limited sources of
animal ingredients containing retinol and beta carotene (meat and
dairy products such as milk, eggs, and their derivatives) are typically
followed in the belief they will offer better control or prevention of
certain diseases or improve general health(32-35).
Exclusively vegetarian diets particularly put children and pregnant
woman at increased risk of hypovitaminosis A as the conversion of
beta carotenes present in vegetables to retinol is limited during di-
gestion and the availability of vitamin A for absorption and hepatic
storage is <20% of dietary vitamin A content(1).
The so-called cafeteria diet or competitive food, based on re-
freshing sodas and industrialized food, is predominantly composed
of carbohydrates and lipids of vegetal source and provides insuffi-
cient amounts of dietary vitamin A. Accordingly, such diets could be con-
sidered causes of hypovitaminosis A and associated ocular problems
in patients with excessive habits related to these diets(36).
The second group of causes of hypovitaminosis A includes the
psychiatric eating disorders, anorexia, and bulimia nervosa, recogni-
zed as major, growing health problems with severe clinical compli-
cations, and high mortality. Both can cause hypovitaminosis A due
to chronic dietary disturbances. The complexity of such conditions
must be recognized in the context of early signs of xerophthalmia
and should be managed in parallel with psychiatric specialists(37,38).
Bariatric techniques for the treatment of obesity include jejunoi-
leal bypass and stomach reduction to induce weight loss by malab-
sorbtive and restrictive mechanisms(39-41). Patients require vitamin su-
pplementation following these procedures; however, a recent study
in Brazil demonstrated that even before bariatric surgery a re lative
amount of patients already have hypovitaminosis A, and that this pre-
valence increases 30 and 180 days after the procedure(42). In patients
with no compliance for a period of weeks or months, ophthalmolo-
gists may evaluate the initial manifestations of hypovitaminosis A.
Special attention should be paid to patients undergoing oculoplastic
or refractive surgeries as their nutritional status may be subclinical
Figure 2. Classic and modern causes of hypovitaminosis A.
Table 2. Major causes of hypovitaminosis A and diagnosis guidelines
Major causes of deciency of vitamin A Description
Primary deficiency Low dietary intake of vitamin A
Food source: liver beef, damascus, spinach, cabbage, milk, carrot, and butter
Diagnosis: food intake history, liver function, and vitamin A serum levels
Restrictive and monotonous diets Restricted intake of sources of vitamin A and consumption of the same group of food for many months
Eating disorders: psychiatric, cafeteria diet, and vegetarian
Diagnosis: food intake history. Physical signs. Blood vitamin A levels
Malabsorption syndrome Reduction in uptake and mucosa transport of digested nutrients to the blood stream
Diagnosis: diarrhea, steatorrhea, weight loss, anemia, hyperkeratosis, and acrodermatitis. Blood examination to check
pancreas and liver function. Stool analysis (fat, parasites)
Bariatric surgery Surgery to treat obesity and associated diseases is divided into restrictive, disabsorptive, and mixed techniques and
often mimics malabsorption syndrome
Diagnosis: surgical history, use of vitamin supplements, bowel habits. Food intake history. Physical signs. Blood levels
of vitamin A. Stool analysis (fat)
Short bowel syndrome Mesenteric vascular disease typically caused by congenital obstruction, thrombosis, and other diseases requiring
bowel resection
Diagnosis: diarrhea, fatigue. Blood levels of vitamin A. Stool analysis (fat)
Liver failure Loss of liver digestive and storage functions due to alcohol toxicity, virus infection, or other causes. Malabsorption
mechanisms and signs may be present.
Diagnosis: blood levels of liver enzymes and vitamin A, virus serology. Stool analysis (fat)
Chronic pancreatitis Loss of pancreas exocrine function affecting digestion. Malabsorption mechanisms and signs may be present
Diagnosis: blood levels of pancreas enzymes and vitamin A. Stool analysis (fat)
Cystic fibrosis Inherited disease affecting chloride channels leading to exocrine gland dysfunction. Malabsorption mechanisms and
signs may be present
Diagnosis: low weight gain in infancy, progressive malnutrition, chronic cough with hypersecretion, chronic sinusitis,
biliary cirrhosis, diabetes, respiratory infections and infertility. Sodium and chloride levels in sweat
Salivary and deglutition diseases Swallowing problems due to xerostomia, tooth problems, and/or muscular deglutition dysfunction. Example: Sjögren’s
Diagnosis: oral and dental examination and salivary flow rate
and cause disturbances in ocular surface homeostasis and wound
healing leading to poor outcomes and serious ocular com plicat ions(40).
Patients with the above-mentioned conditions may share a number
of characteristics including individual concern and anxiety regarding
body image, health, and satisfaction with food consumption.
The fourth class of modern causes of hypovitaminosis A that may
contribute to or worsen ocular surface diseases is the chronic disease
leading to chronic impairment of the organs involved in digestion
and clearance of vitamin A metabolites (Figure 1). Although the
ma jority of these diseases are not new, improvements in therapeutic
approach have allowed affected patients to lead longer and more acti-
ve lives. Similarly, vitamin A deficiency may be neglected in patients
receiving frequent healthcare.
Within this group, the diseases causing severe dry mouth, such
as head and neck radiotherapy and Sjögren’s syndrome, may limit
deglutition and digestion and impose dietary restrictions that may
lead to hypovitaminosis A(43,44). Therefore, dietary habits and vitamin
A levels should be evaluated in patients presenting the diseases des-
cribed above and ocular surface complications. Although patients
commonly present with dry eye disease associated with these con-
ditions, the clinical picture may be aggravated by hypovitaminosis A.
Renal failure and hemodialysis are associated with dry eye disease
and ocular surface changes in diabetic and nondiabetic patients(45,46).
There is currently controversy regarding lower vitamin A levels in
such patients as renal failure reduced the reliability of traditional me-
thods of measuring vitamin A levels. However, lower blood vitamin
A levels have been shown to be associated with higher morbidity and
mortality in these patient populations(47,48). Recently, a case of night
blindness and compatible retinal changes was described in a he-
modialysis patient with apparent normal levels of serum retinol that
were corrected with retinol palmitate treatment(49).
sIDe effeCTs Of vITAMIN A MeDICAl Use
The utility of vitamin A topical eye drop administration in treating
dry eye has been comprehensively investigated(50,51). Vitamin A topi-
cal eye drops may also have utility in the treatment of skin diseases
and specific types of cancer including ocular surface neoplasia(52,53).
However, excessive vitamin A intake is known to induce gastric and
neural side effects such as abdominal and head pain, nausea, and
irritability(54,55). These symptoms may be aggravated by chronic use of
vitamin A eye drops and lead to the development of blurred vision and
pseudotumor cerebri(56-58). A clinical history of dry skin and mucosa,
nausea, and retinoic acid intake in meals or pharmaceutical formu-
lations should inform suspicion of acute and chronic side effects or
consequences of excessive vitamin A dosing.
Recently, two publications reviewed the mechanisms underlying
the induction of meibomian gland dysfunction and dry eye symptoms
by systemic retinoic acid therapy for acne. The authors discussed
the effects of systemic and topical skin or ocular application of diffe-
rent forms and doses of vitamin A formulations. Moreover, it was
persistent meibomian gland dysfunction after systemic retinoic acid
discontinuation was reported(4,52).
CAse RepORTs
Case report 1: A 2-year-old boy presented with a history of con-
se cutive episodes of hordeola affecting the upper and lower lids of
both eyes over the preceding 12 months. The patient had a history
of photophobia and crying without tears. Previous ocular treatment
included lubricants and antiallergic eye drops. The patient was an
only child with no other personal or family antecedents. His dietary
habits were based on soft drinks and junk food between meals with
deficient intake of meat, milk derivatives, vegetables, and fruits.
Swollen lids and hordeola affecting both eyes were observed on exa-
mination. He was able to fix and follow light projection with both eyes
but was unable to perform visual acuity testing. Slit lamp examination
demonstrated mild punctate keratitis and an epithelial defect in the
right cornea. The rest of the ocular examination was normal. His
body weight matched the 50th percentile for age and sex (12.7 kg);
however, his height was in the tenth percentile (84 cm). Laboratory
testing was requested and identified hypochromic and microcytic
anemia with low blood levels of iron and retinol (32.7 μg/dl and
0.20 mg/l, where the normal levels for children are 50-150 μg/dl
and 0.30-0.80 mg/l, respectively).
Clinical findings and laboratory testing indicated the chronic pre-
sence of hordeola, syndrome sicca, growth retardation, and anemia
were all consequences of a diet deficient in essential elements such
as vitamin A and iron (Fe). The diet was reoriented, and the child was
maintained under close observation by his pediatrician until clinical
signs improved fully.
Case report 2: A 71-year-old woman presented with decreased
vision and pain in the left eye (OS) for 20 days and a diagnosis of
corneal ulcer. She was receiving antibiotic and corticosteroids eye
drops at the time of presentation. She had previously undergone
cataract surgery in both eyes 2 months prior to this presentation.
Her medical history was noncontributive except for inappetence and
weight loss of approximately 10 kg over the preceding year. Her visual
acuity was 0.5 in her right eye (OD) and counting fingers at 1 m OS.
Biomicroscopic examination revealed conjunctiva hyperemia and a
1.5 mm by 2.5 mm corneal ulcer without secretion or infiltration. A
diagnosis of microbial keratitis was made, and eye drops were chan-
ged accordingly. During follow-up, she developed a corneal ulcer OD
and the ulcer in the OS worsened. Severe corneal punctate fluores-
cein staining and conjunctival Rose Bengal staining were observed
in both eyes. The Schirmer test without anesthesia was zero in both
eyes. Her salivary flow was 0.06 ml/min (normal values >0.1 ml/min;
Figure 3). Laboratory tests were positive for SSa and SSb (anti-Ro and
anti-La antibodies, respectively), and blood levels of vitamin A were
0.2 mg/l. A minor salivary gland biopsy demonstrated leukocyte infil-
tration with focal organization, ductal dilation, and extensive fibrosis
replacing acinar structures. The focus score was graded 4. During eva-
luations, the patient developed corneal melting OD and underwent
penetrant keratoplasty. The present findings indicated a diagnosis of
Sjögren’s syndrome aggravated by hypovitaminosis A. After a period
of corticosteroids and vitamin A therapy, her general and ocular
symptoms improved. Her case illustrates a delicate combination of
causes of sicca syndrome (Sjögren’s syndrome and hypovitaminosis
A) leading to a severe presentation. The extensive fibrosis of salivary
gland structures, almost completely replaced by fibrosis, may be a
consequence of concurrent disease and ageing (Figure 3 D).
Case report 3: A 22-year-old woman presented with ocular pain,
lid edema, and thick tearing for 5 months not improved by lubricants,
cyclosporine eye drops, or bandage contact lenses. She reported a
habit of mucous fishing. Her previous medical history included myo-
pia, allergy, and acne vulgaris. She had been prescribed a 6-month
course of oral isotretinoin 6 years previously without side effects
and again 6 months prior to the current complaint. Examination
revealed skin scarring, meibomian gland dysfunction, and punctate
and filamentary keratitis that was worse OD (Figure 4). The tear film
breakup time was 3 s in both eyes and the tarsal conjunctiva presen-
ted papillary reaction. The Schirmer test without anesthesia was zero
in OD and 2 mm in OS, and her salivary flow rate was 0.033 ml/min.
Laboratory testing was negative for hormonal abnormalities, and
cystic fibrosis and her vitamin A blood levels were 0.4 mg/l. Tests for
autoimmune diseases were negative for SSa and SSb, rheumatoid
factor, and antinuclear antibody. Her condition was attributed to
a side effect of isotretinoin treatment that had persisted after an
18-month interruption of oral isotretinoin intake. Her case corrobo-
rates previous reports of vitamin A-induced dry eye and represents a
severe form of this condition that persisted after discontinuation of
the causative medication.
 
Hypovitaminosis A should be suspected in all cases of night blindness,
ocular surface foreign body sensation, and photophobia without other
evident causes. Crying without tearing is another relevant symptom of
hypovitaminosis A. Recurrent hordeolum, meibomian gland dysfunc-
tion identified by gland dropout or inflammation with thickened lipid
secretion, corneal epithelial defect, conjunctiva metaplasia (where
Bitot’s spot is an advanced form and a hallmark), and diffuse punctate
keratitis also represent signs suspicious for hypovitaminosis A.
In all patients suspected to have hypovitaminosis A, a dietary intake
and nutritional habits enquiry must be conducted, with previously
validated evaluation models available. In children, investigations of
height and weight gain during the management period may also
have utility.
The utility of blood vitamin A levels measurements is broadly
accepted, and a classification system established by the World Health
Organization has defined low vitamin A levels as serum retinol con-
centrations <0.3 mg/l or 0.7 µM. There have been concerns regarding
the reliability of blood concentration measurements as the liver is
able to sustain normal levels even in extremely vitamin A-deficient
Other blood tests including complete blood count, protein, albu-
min, micronutrients, electrolyte concentrations, and stool fat micros-
copy have all demonstrated utility in assessing vitamin A deficiency
severity. In addition, liver function tests, serology for hepatitis, and
sweat sodium chloride test values >60 mM may aid in distinguishing
between liver diseases and cystic fibrosis, respectively.
Ocular surface assessments may be performed with vital staining
and tear secretion measurements (fluorescein dye and Schirmer’s
test). Corneal and conjunctival impression cytology allows documen-
tation of ocular surface epithelial metaplasia, square and speculate
cells morphology, reduced nuclear size, and the absence or paucity
of goblet cells on microscopy. Ocular surface assessments have de-
monstrated utility as simple and mildly invasive methods of recor-
ding and monitoring hypovitaminosis A in early xerophthalmia(61).
The major aim of treatment is to restore vitamin A levels in cases
of hypovitaminosis and reduce exposure in conditions associated
with side effects of oral or skin topical vitamin A use. Details regarding
dosage and administration routes are outside the scope of the pre-
sent review, as they are dependent on the underlying cause, patient
characteristics, and severity of individual cases.
Healthcare professionals attending poor populations and pa-
tients with chronic malabsorption syndrome, hepatic, and other re-
lated diseases should be familiar with the classic causes of hypovita-
minosis A. The modern causes of hypovitaminosis A do not have the
same magnitude in terms of prevalence but should be considered
by ophthalmologists in daily clinical practice. Hypovitaminosis A can
cause blindness and corneal opacity, but it is also an important cause
of morbidity and mortality.
Increased suspicion of hypovitaminosis A due to ocular surfa ce
symptoms and signals should direct prompt investigation of nu tritional
and digestive problems followed by interdisciplinary management
allowing early diagnosis and treatment of the causes and effects of
the majority of diseases related to hypovitaminosis A.
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Figure 3. A 71-year-old woman with bilateral corneal ulcers, weight loss, and features
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... Although the body stores vitamin A as retinyl ester in liver and to a lesser extent in adipose, lung, and other tissues, these stores may become depleted over time if the diet is consistently deficient in vitamin A, or stores may never develop in children who are not adequately breastfed and/or do not receive an adequate diet after weaning (141). Food deprivation, unbalanced diet, and malabsorption syndromes are the most common causes of deficiency (142)(143)(144). Worldwide, dietary deficiency is by far the most common cause, epidemic in developing countries and particularly affecting young children (145,146). ...
... Worldwide, dietary deficiency is by far the most common cause, epidemic in developing countries and particularly affecting young children (145,146). Dietary deficiency may also be observed in individuals with low general food intake, such as in anorexia or bulimia nervosa (142). Fat malabsorption syndromes can result in hypovitaminosis A, such as due to chronic pancreatitis, inflammatory bowel disease, and liver disease (142,147). ...
... Dietary deficiency may also be observed in individuals with low general food intake, such as in anorexia or bulimia nervosa (142). Fat malabsorption syndromes can result in hypovitaminosis A, such as due to chronic pancreatitis, inflammatory bowel disease, and liver disease (142,147). ...
Full-text available
The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt's disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt's or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A's functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis.
... A.M.'s clinical presentation suggests vitamin A deficiency. 4 The classic presentation of vitamin A deficiency is dryness of the eyes and night blindness. [16][17][18] Vitamin A deficiency is most commonly associated with prolonged malnutrition in developing countries, especially in times of famine, but may occur acutely in individuals with eating disorders or malabsorption syndromes. 18,19 The diet in the 18th century was probably less balanced than modern diets in developed countries and may be comparable with diets in the modern developing world. ...
In 1755 in Bergemoletto, Italy, an avalanche buried 4 people (2 women, a girl, and a boy) and several animals in a stable. After 37 d in a pitch-dark confined space, 3 of the 4 people were rescued alive. The 3 survivors had only goat milk, a few chestnuts, a few kg of raw kid meat, and meltwater for nutrition. We describe the longest-known survival in an avalanche burial and discuss the medical and psychological problems of the survivors. The boy died. When they were extricated, all 3 survivors were exhausted, cachectic, and unable to stand or walk. They were severely malnourished and were experiencing tingling, tremors, and weakness in the legs; constipation; changes in taste; and amenorrhea. One of the women had persistent eye problems and developed symptoms consistent with post-traumatic stress disorder. The survivors were given slow refeeding. It took from 1 to 6 wk before they could walk. We compare this case to other long-duration burials, especially mining accidents, and describe the rescue and patient care after long-duration burials. This case demonstrates that people can overcome extremely adverse conditions and survive.
... Vitamin A deficiency can lead to blindness and cutaneous aberrations, can make a person prone to infections, and can increase the risk of cancer development [97]. As dangerous as deficiency is, the excessive intake of vitamin A can lead to neurological side effects, osteoporosis, and abnormalities during embryogenesis [98][99][100]. ...
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There has been considerable interest in dietary supplements in the last two decades. Companies are releasing new specifics at an alarming pace, while dietary supplements are one of the less-studied substances released for public consumption. However, access to state-of-the-art and high-throughput techniques, such as the ones used in omics, make it possible to check the impact of a substance on human transcriptome or proteome and provide answers to whether its use is reasonable and beneficial. In this review, the main domains of omics are briefly introduced. The review focuses on the three most widely used omics techniques: NGS, LC-MS, NMR, and their usefulness in studying dietary supplements. Examples of studies are described for some of the most commonly supplemented substances, such as vitamins: D, E, A, and plant extracts: resveratrol, green tea, ginseng, and curcumin extract. Techniques used in omics have proven to be useful in studying dietary supplements. NGS techniques are helpful in identifying pathways that change upon supplementation and determining polymorphisms or conditions that qualify for the necessity of a given supplementation. LC-MS techniques are used to establish the serum content of supplemented a compound and its effects on metabolites. Both LC-MS and NMR help establish the actual composition of a compound, its primary and secondary metabolites, and its potential toxicity. Moreover, NMR techniques determine what conditions affect the effectiveness of supplementation.
... Vitamin A is essential in a wide spectrum of physiological activities such as clear retinal vision [13], skin health [14], immune system [15], reproduction [16], and embryonic development as previously reviewed in [16][17][18][19]. ...
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Age and Gender are vital determinants for the micronutrient demands of normal indviduals. Among these micronutrients are vitamins that are required in small amounts for optimum metabolism, homeostasis, and a healthy lifestyle, acting as coenzymes in several biochemical reactions. The majority of previous studies have examined such issues that relates to a specific vitamin or life stage, with the majority merely reporting the effect of either excess or deficiency. Vitamins are classified into water-soluble and fat-soluble components. The fat-soluble vitamins include vitamins (A, D, E, and K). Fat-soluble vitamins were found to have an indisputable role in an array of physiological processes such as immune regulation, vision, bone and mental health. Nonetheless, the fat-soluble vitamins are now considered a prophylactic measurement for a multitude of diseases such as autism, rickets disease, gestational diabetes, and asthma. Herein, in this review, a deep insight into the orchestration of the four different fat-soluble vitamins requirements is presented for the first time across the human life cycle beginning from fertility, pregnancy, adulthood, and senility with an extensive assessment ofthe interactions among them and their underlying mechanistic actions. The influence of sex for each vitamin is also presented at each life stage to highlight the different daily requirements and effects.
... Subyek yang kekurangan vitamin A menunjukkan waktu yang lebih lama untuk "break rod-cone", yang dapat terjadi sebelum gejala rabun senja. Dengan defisiensi vitamin A yang berlanjut, permukaan konjungtiva menjadi kering, bergelombang, permukaan tidak beraturan, akhirnya mengembangkan lapisan putih, berbusa, atau bahan "cheesy" yang terdiri dari keratin yang terdeskuamasi dan pertumbuhan bakteri yang berat (Faustino et al., 2016 ...
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Pengetahun tentang Gizi mutlak diperlukan dan bermanfaat terhadap pemilihan makanan sehari-hari, agar semua zat gizi yang dibutuhkan oleh fungsi normal tubuh dapat terpenuhi. Selain itu dengan mempelajari ilmu gizi bermanfaat pula untuk mengetahui status gizi masyarakat serta upaya penanggulangan masalah gizi yang terjadi di masyarakat/populasi penduduk Buku ini diharapkan dapat dijadikan referensi/sumber rujukan dalam upaya pemenuhan gizi bagi tubuh, yang tertuang dalam beberapa bab berikut ini: Bab 1 Konsep Dasar Ilmu Kesehatan Masyarakat Bab 2 Gizi dan Ruang Lingkupnya Bab 3 Gizi, Pencernaan dan Alat Pencernaan Bab 4 Makanan, Zat Makanan, dan Fungsinya bagi Tubuh Bab 5 Karbohidrat dan Metabolismenya Bab 6 Protein dan Metabolismenya Bab 7 Vitamin dan Metabolismenya Bab 8 Mineral dan Metabolismenya
... Specifically, vitamins A, D, and E are readily bioavailable in fish oils like cod liver oil and in (fish) species like sardine, mackerel, herring, lake trout, and salmon [58]. Vitamin A sustains normal growth, builds cells, and promotes good eyesight [93], yet dependent on the form in which they exist. Retinol, for instance, is converted in the body to 11-trans-retinal via an oxidative process, whereas the 11-trans-retinal is subsequently isomerized into 11-cis-retinal, which is the functional form of the vitamin essential for vision/visual physiology [94]. ...
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Global public awareness about fish-based diet and its health/nutritional benefits is on the rise. Fish nutritional profile projects promising bioactive and other compounds with innumerable health benefits for human wellbeing. As various reported researches involving fish/marine-derived molecules reveal promising attributes, and as the position of fish-based nutrients as nutraceuticals continue to strengthen, health challenges still confront communities worldwide, from cardiovascular disease, diabetes, and obesity to hypertension. Thus, further understanding of fish-based nutrient impact as functional foods remains crucial given the diverse prevailing compositional/nutraceutical merits. In this review, therefore, we provide important information regarding bioactive compounds and therapeutics obtained from fish, specific to the context of their suitability in functional foods to enhance human health. This contribution is hereby constructed as follows: (a) fish nutraceutical/therapeutic components, (b) constituents of fish-based nutrients and their suitability in functional foods, (c) fish antioxidant/bioactive compounds to help alleviate health conditions, (d) common human ailments alleviated by fish-based nutrients, and (e) role of fish in mental health and immune system. As increased fish consumption should be encouraged, the potential of the quality proteins, omega-3 fatty acids, and other compounds inherent in fish should steadily be harnessed.
... The VA is crucial in the human body as it enhances a stronger immune system, developmental functions, and proper eyesight (Faustino et al., 2016;Mishra & Singh, 2010;Obeng-bio et al., 2019). Inadequate intake of VA in the human body leads to opportunistic diseases generally referred to as vitamin A deficiency (VAD) (Sheoran et al., 2022;Wurtzel, 2004). ...
Maize is among the crops containing carotenoids that are easily converted to vitamin A and have an enormous influence on consumers' health. Principally maize has high calories and proteins but has less number of other micronutrients such as vitamin A. Societies that use maize as their main and sole staple food are likely to be affected by vitamin A deficiency. Thus, development and production of maize varieties rich in micronutrients and vitamin A are important for improved health. This study characterized 5 carotenoid components in maize genotypes grown in Tanzania as a strategy for improving vitamin A content in maize. The study involved maize landraces, commercial or elite varieties, and inbred lines in determining their potential for provitamin A breeding programs for nutrition improvement. The study found that mean concentration of important carotenoid components, i.e., alpha carotene (AC), beta-carotene (BC), beta-cryptoxanthin (BCX), lutein (LU), zeaxanthin (ZX), provitamin A (ProVA), non-provitamin A (Non-ProVA), and total carotenoids (TC) varied significantly (P<0.001) among maize genotypes. The 3 maize groups studied (landraces, commercial varieties, and breeding materials (BMs) varied significantly. For maize landraces, the concentration (µg/g) of studied carotenoids were AC (0.13-2.67), BC (0.60-3.72), BCX (0.36-1.01), ProVA (0.89-5.29), Retinol (0.25-0.87), LU (2.37-16.97). ZX (0.16-4.41), Non-ProVA (2.4-19.01), and TC (3.68-25.27); in commercial or elite maize varieties were (in µg/g): AC (0.31-3.84), BC (0.56-6.5), BCX (0.46-2.58), ProVA (0.92-11.80), Retinol (0.15-1.82), LU (3.28-22.39). ZX (0.05-11.31), Non-ProVA (2.56-28.81), and TC (4.23-37.84); and for maize BMs AC (0.53-6.64), BC (1.92-13.87), BCX (0.65-6.51), ProVA (2.69-18.62), Retinol (0.5-3.1), LU (4.86-34.99). ZX (0.06-18.58), Non-ProVA (4.8-53.57), and TC (9.86-76.94). Furthermore, the study found that the concentration of studied carotenoids was higher in pigmented (yellow or red) maize genotypes than in white maize genotypes. The current study found an appreciable amount of ProVA in studied materials, including maize landraces, commercial yellow varieties, and CIMMYT lines. The concentration of ProVA and retinol determined in studied maize genotypes were below 15 µg/g a daily vitamin A requirement, thus based on the current ProVA and retinol status it is difficult to meet Vitamin A requirement. Therefore, these maize genotypes with promising levels of carotenoid components are potential breeding materials that can be used in maize provitamin A biofortification program for improved food nutrition and livelihoods in Tanzania.
... The prevalence of each condition varies on the population. 5 Therefore, early and specific questioning to explore the ...
... The causes of hidden hunger involve socioeconomic parameters, cultural habits, modern methods of food production, storage, and processing, and individuals' health status (Bawa and Anilakumar 2013;Faustino et al., 2016;Faustino et al., 2018;Gödecke et al., 2018;Trono 2019). Genetic modification to produce food crop biofortification enriched for Fe, Zn, and vitamin A is an initiative to revert the global imbalance between an excessive caloric diet versus micronutrient malnutrition. ...
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Oxidative stress (OS) is a major disruption in the physiology of the lacrimal functional unit (LFU). Antioxidant enzymes have dual protective activities: antioxidant and antimicrobial activities. Peroxidases have been indistinctly used as markers of the secretory activity of the LFU and implicated in the pathophysiology, diagnosis and treatment of dry eye disease (DED), even though they comprise a large family of enzymes that includes lactoperoxidase (LPO) and glutathione peroxidase (GPO), among others. Assays to measure and correlate OS with other local LFU phenomena have methodological limitations. Studies implicate molecules and reactions involved in OS as markers of homeostasis, and other studies identify them as part of the physiopathology of diseases. Despite these conflicting concepts and observations, it is clear that OS is influential in the development of DED. Moreover, many antioxidant strategies have been proposed for its treatment, including calorie restriction to nutritional supplementation. This review offers a critical analysis of the biological mechanisms, diagnostic outcomes, drug use, dietary supplements, and life habits that implicate the influence of OS on DED.
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Dry eye syndrome (DES) is multifactorial and likely to be a cause of concern more so than ever given the rapid pace of modernization, which is directly associated with many of the extrinsic causative factors. Additionally, recent studies have also postulated novel etiologies that may provide the basis for alternative treatment methods clinically. Such insights are especially important given that current approaches to tackle DES remains suboptimal. This review will primarily cover a comprehensive list of causes that lead to DES, summarize all the upcoming and ongoing clinical trials that focuses on treating this disease as well as discuss future potential treatments that can improve inclusivity.
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Vitamin A (retinol) and its congeners - the retinoids - participate in a panoply of biological events, as for instance cell differentiation, proliferation, survival, and death, necessary to maintain tissue homeostasis. Furthermore, such molecules may be applied as therapeutic agents in the case of some diseases, including dermatological disturbances, immunodeficiency, and cancer (mainly leukemia). In spite of this, there is a growing body of evidences showing that vitamin A doses exceeding the nutritional requirements may lead to negative consequences, including bioenergetics state dysfunction, redox impairment, altered cellular signaling, and cell death or proliferation, depending on the cell type. Neurotoxicity has long been demonstrated as a possible side effect of inadvertent consumption, or even under medical recommendation of vitamin A and retinoids at moderate to high doses. However, the exact mechanism by which such molecules exert a neurotoxic role is not clear yet. In this review, recent data are discussed regarding the molecular findings associated with the vitamin A-related neurotoxicity.
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Current evidence suggests that only bariatric surgery results in durable and substantial weight loss with resolve various comorbid medical conditions, improve quality of life, and prolong survival for patients with morbid obesity. Demand for bariatric surgery is increasing worldwide at an exponential rate. With rapid rise of morbidly obese patients, introduction of laparoscopy, use of mass media and internet to convey information to public, coverage of medical insurance might contribute to the Bariatric revolution. Bariatric surgery involve either restrictive of caloric intake or malabsorption of nutrients, or both. Bariatric surgery would bring about neurohormonal changes that affect satiety and glucose homeostasis as well. Laparoscopic adjustable gastric banding, laparoscopic Roux-en-Y gastric bypass, biliopancreatic diversion with/without duodenal switch, and laparoscopic sleeve gastrectomy are the most commonly performed procedures at present. Each procedure has its advantages and disadvantages and any operative procedure cannot be thought to be predominant over another. We hope more effective, safer, and durable operative method to be developed. The author intended to provide a comprehensive overview of the current status of bariatric surgery.
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Vitamin A deficiency (VAD) can cause a range of ocular manifestations, including night blindness, conjunctival and corneal xerosis and keratomalacia. It is an important cause of preventable blindness. Although usually a result of malnutrition, VAD can accompany malabsorption syndrome. We report a case of VAD as manifested by Bitot's spots and eventually diagnosed to have celiac disease. It is, therefore, important to consider gastrointestinal diseases causing malabsorption in the evaluation of VAD.
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Objectives: To evaluate dry eye symptoms and clinical tear film alterations in patients with chronic renal failure (CRF). Materials and methods: Thirty-five non-diabetic CRF patients undergoing hemodialysis, and 31 healthy individuals were enrolled. An ocular surface disease index questionnaire (OSDI) was administered, and after a complete ocular examination, Schirmer and tear break-up time (TBUT) tests were performed. Results: OSDI scores were significantly higher (p<0.01) and TBUT tests were significantly lower (p=0.01) in CRF patients than in the control group. Schirmer test results were also lower in the CRF patients group, but lacked statistical significance (p=0.20). Conclusion: Patients with CRF should be advised to obtain an ophthalmic examination, especially for dry eye.
Conference Paper
Comprehensive recommendations for the assessment and control of vitamin A deficiency (VAD) were rigorously reviewed and revised by a working group and presented for discussion at the XX International Vitamin A Consultative Group meeting in Hanoi, Vietnam. These recommendations include standardized definitions of VAD and VAD disorders. VAD is defined as liver stores below 20 mug (0.07 mumol) of retinol per gram. VAD disorders are defined as any health and physiologic consequences attributable to VAD, whether clinically evident (xerophthalmia, anemia, growth retardation, increased infectious morbidity and mortality) or not (impaired iron mobilization, disturbed cellular differentiation and depressed immune response). An estimated 140 million preschool-aged children and at least 7.2 million pregnant women are vitamin A deficient, of whom >10 million suffer clinical complications, principally xerophthalmia but also increased mortality, each year. A maternal history of night blindness during a recent pregnancy was added to the clinical criteria for assessing vitamin A status of a population, and the serum retinol criterion for a "public health problem" was revised to 15% or more of children sampled having levels of <20 mug/dL (0.7 mumol/L). Clinical trials and kinetic models indicate that young children in developing countries cannot achieve normal vitamin A status from plant diets alone. Fortification, supplementation, or other means of increasing vitamin A intake are needed to correct widespread deficiency. To improve the status of young infants, the vitamin A supplements provided to mothers during their first 6 wk postpartum and to young infants during their first 6 mo of life should be doubled.
: The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.
Retinoic acid is known to improve cutaneous wound healing and, in recent years, its application in ophthalmology has been investigated. This review looks at the role of retinoic acid on the ocular surface. Retinoic acid can be produced synthetically, and its mechanism of action includes both nuclear and non-nuclear receptor mediated pathways. It has been shown to improve full and partial thickness corneal lacerations as well as corneal epithelial defects. Retinoic acid plays a critical role in cell differentiation at the cornea, conjunctiva, and limbus, and may have an anti-tumor role. Its positive effect is only achieved at the correct concentration, however; excess concentrations of retinoic acid have a deleterious effect. The main limiting factor of retinoic acid use is its detrimental effect on meibomian glands, resulting in cell death, atrophy of acini, hyposecretion of oils, and altered gene expression, eventually resulting in dry eye symptoms. This effect is reversible on discontinuation of the drug. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
• An emaciated alcoholic 52-year-old white woman presented with an old left corneal perforation and bilateral conjunctival and corneal xerosis. The serum vitamin A level was 0 μmol/L. Laboratory and radiologic findings were consistent with the diagnosis of a fat malabsorptive syndrome secondary to chronic alcoholic pancreatitis. Histopathologic evaluation of her enucleated globe revealed conjunctival epidermidalization, corneal perforation with prolapse and loss of intraocular contents, retinal detachment, and massive choroidal hemorrhage. A second patient presented with bilateral conjunctival xerosis, corneal ulcers, and a low serum vitamin A level. Corneal perforation of one ulcer ensued during her hospitalization. Medical investigation revealed hepatic metastases of an unknown primary source. Causes of vitamin A deficiency and its ocular complications as well as medical and surgical management options are discussed.
As a part of the visual cycle, all-trans-retinol (all-trans-ROL), the major form of vitamin A in circulating blood, is transported to the retinal pigment epithelium (RPE). All-trans-ROL is essential for normal retina function. However, recent researches have shown that excessive retinol intake can cause increase of all-trans-retinal. This can lead to the accumulation of lipofuscin, which is important in the pathogenesis of retina degeneration disease, such as dry type age-related macular degeneration (AMD). Since there are few reports regarding the involvement of all-trans-ROL in exudative AMD, we investigated the effects of all-trans-ROL in vitro and in vivo. We evaluated vascular endothelial growth factor (VEGF) expression in ARPE-19 cells and THP-1 cells after all-trans-ROL treatment using ELISA and real-time RT-PCR. In-vitro tube formation assay was performed with HUVEC cells using the conditioned medium (CM) obtained from ARPE-19 cells treated with all-trans-ROL. Transcriptional activity of retinoic acid receptor (RAR) was evaluated using luciferase assay. In mice, VEGF expressions were investigated in the retina and RPE/choroid after three weeks of excessive oral retinol intake. Laser-induced choroidal neovascularization (CNV) models were evaluated after they were fed with various doses of retinol. VEGF mRNA expression and VEGF production were significantly increased in all-trans-ROL treated ARPE-19 cells, which were inhibited by an RAR antagonist LE540. In contrast, there were no significant changes in VEGF production in THP-1 cells. Transcriptional activity of RAR was upregulated by all-trans-ROL treatment in ARPE-19 cells. The CM, obtained from ARPE-19 cells treated with all-trans-ROL, induced more capillary-like tube formation than cells treated with control vehicles. In vivo, the high retinol diet group has increased VEGF expression in the RPE/choroid and larger lesion size was induced. Our results suggest that all-trans-ROL is a pro-angiogenic factor. Excessive retinoid intake may be a potential risk factor for exudative AMD. Copyright © 2015. Published by Elsevier Ltd.