Eye color is a polygenic trait and is determined primarily by the amount and type of pigments in the eye's iris.^[1][2] Humans and animals have many phenotypic variations in eye color.^[3] In humans, these variations in color are attributed to varying ratios of eumelanin produced by melanocytes in the iris.^[2] The brightly colored eyes of many bird species are largely determined by other pigments, such as pteridines, purines, and carotenoids.^[4]

Three main elements within the iris contribute to its color: the melanin content of the iris pigment epithelium, the melanin content within the iris stroma, and the cellular density of the iris stroma.^[5] In eyes of all colors, the iris pigment epithelium contains the black pigment, eumelanin.^[2][5] Color variations among different irises are typically attributed to the melanin content within the iris stroma.^[5] The density of cells within the stroma affects how much light is absorbed by the underlying pigment epithelium.^[5]

Determination of eye color

Eye colors can range from most common, brown, to least common, green. Rare genetic mutations can even lead to unnatural eye colors like black, red, and violet. Natural eye colors include brown(being most common), then hazel, blue, grey, and green. Unnatural eye colors include red, black,and violet. Eye color is an inherited trait influenced by more than one gene.^[6][7] Two major genes and multiple minor genes account for the tremendous variation of human eye color.^[8] In humans, three genes associated with eye color are currently known: EYCL1, EYCL2, and EYCL3.^[9][10] These genes account for three phenotypic eye colors (brown, green, and blue) in humans.^[3] Eye color usually stabilizes when an infant is around 6 months old.^[11]

In 2006, the molecular basis of the EYCL3 locus was resolved.^[12] In a study of 3839 people, researchers reported that 74% of total variation in eye color was explained by a number of single nucleotide polymorphisms (SNPs) near the OCA2 gene (OMIM: 203200). OCA2 was previously known because, when mutated, the gene can result in a type of albinism. The recent study showed that different SNPs strongly associate with blue and green eyes as well as variations in freckling, mole counts, hair and skin tone. The authors speculate that the SNPs may be in an OCA2 regulatory sequence and thus influence the expression of the gene product, which in turn affects pigmentation.^[13] A 2008 study demonstrated that a specific mutation within the HERC2 gene that regulates OCA2 expression is responsible for blue eyes^[14] (see below).

Blue eyes with a brown spot, Green eyes and Gray eyes are caused by an entirely different part of the genome. As Eiberg said: "The SNP rs12913832 is found to be associated with the brown and blue eye color, but this single DNA variation cannot explain all the brown eye color variation from dark brown over hazel to blue eyes with brown spots".

Classification of colors

The perception of color depends upon various factors. These are the same eyes; however, depending on the light and surrounding hues, the eye color can appear quite different.

Iris color can provide a large amount of information about an individual and a classification of various colors may be useful in documenting pathological changes or determining how a person may respond to various ocular pharmaceuticals.^[15] Various classification systems have ranged from a basic "light" or "dark" description to detailed gradings employing photographic standards for comparison.^[15] Others have attempted to set objective standards of color comparison.^[16]

As the perception of color is dependent on viewing conditions (e. g. the amount and type of illumination, as well as the hue of the surrounding environment), so is the perception of eye color.^[17]

Eye color exists on a continuum from the darkest shades of brown to the lightest shades of blue.^[6] Seeing the need for a standardized classification system that was simple, yet detailed enough for research purposes, Seddon et. al developed a graded one based on the predominant iris color and the amount of brown or yellow pigment present. There are 3 true colors in the eyes that determine the outward appearance; brown, yellow, and blue. How much of each color you have determines the appearance of the eye color. The color of the eyes in turn depends on how much of these colors are present. For example, green eyes have yellow and some blue, making them appear green. Brown eyes appear brown because most of the eye contains the brown color. The above is true for the species Homo sapiens. The iris color can vary in the animal world. Instead of blue in humans, autosomal recessive color in the species Corucia zebrata is black, whereas the autosomal dominant color is yellow-green.^[18]

Amber

An amber eye

Human amber eyes displaying the yellow pigments.

Amber eyes are of a solid color and have a strong yellowish/golden and russet/coppery tint. This might be due to the deposition of the yellow pigment called "lipochrome" in the iris (which is also found in green and violet eyes).^[19][20] They are nicknamed "Wolf eyes" due to the high rate of the amber eye color in wolves.

The eyes of some pigeons contain yellow fluorescing pigments known as pteridines.^[21] The bright yellow eyes of the Great Horned Owl are thought to be due to the presence of the pteridine pigment xanthopterin within certain chromatophores (called xanthophores) located in the iris stroma.^[22] In humans, yellowish specks or patches are thought to be due to the pigment lipofuscin, also known as lipochrome.^[23]

Blue

A blue eye

Light eyes map

Blue eyes contain low amounts of melanin within the iris stroma; longer wavelengths of light tend to be absorbed by the underlying iris pigment epithelium, and shorter wavelengths are reflected and undergo Rayleigh scattering.^[5] The type of melanin present is eumelanin.^[24] The inheritance pattern followed by blue eyes is considered similar to that of a recessive trait, however it is a polygenic trait (meaning that it is controlled by the interactions of several genes, not just one).^[7] Eiberg and colleagues showed in a study published in Human Genetics that a mutation in the 86th intron of the HERC2 gene, which is hypothesized to interact with the OCA2 gene promoter, reduced expression of OCA2 with subsequent reduction in melanin production.^[25]

The authors concluded that the mutation may have arisen in a single individual around the Black Sea region 6,000-10,000 years ago, perhaps suggesting that all people with true blue eyes are more closely related. However, blue eyes with brown spots around the pupil are not related to this mutation.^[25]

One survey estimated that nearly 90% of Icelanders have blue or green eyes. Blue eyes are often found in Northern European countries, and are most common in Ireland^[26], Germany^[27] , Netherlands^[28], Iceland^[29] , Austria^[30], Sweden^[31], Norway^[32], Denmark^[33], Finland^[34], Estonia^[35], and the United Kingdom^[36][37] They are also present in Southern Europe , in the Middle East (especially in Israel and the rest of the Levant) and are also found in Afghanistan and rarely in India. A 2002 study found the prevalence of blue eye color among Whites in the United States to be 33.8% for those born between 1936 and 1951 compared to 57.4% for those born between 1899 and 1905.^[7]

As melanin production generally increases during the first few years of life (especially if exposed to the sun), the blue eyes of some babies may darken as they get older.^{citation needed}

Brown

Dark brown human iris

In humans, brown eyes contain large amounts of melanin (eumelanin) within the iris stroma, which serves to absorb light, particularly at the shorter wavelengths. Brown is the most common eye color. ^[5][24] Very dark brown irises may appear to be black.^[38][39]

Brown is predominant^[40] and, in many populations, it is (with few exceptions) the only iris color present.^[41] It is less common in countries around the Baltic Sea, such as Finland and Estonia.

Gray

A steel blue-gray eye

Female gray eyes

Male gray eyes

Gray eyes have less melanin than blue eyes, even though they are considered a darker shade of blue (like blue-green). They are most common in European Russia, Finland and the Baltic States. Under magnification, gray eyes exhibit small amounts of yellow and brown color in the iris.

A gray iris may indicate the presence of a uveitis. However, other visual signs make a uveitis obvious.

Visually, gray eyes often tend to appear to change between the shades of blue, green and gray. This is said to be influenced by the lighting and the surroundings (such as clothes, makeup, etc.).

The Greek goddess Athena was renowned for having "owl-gray" (in Greek, γλαυκῶπις – glaukōpis) or "sea-gray" eyes.^[42]

Green

Green eyes

Green eyes are the product of moderate amounts of melanin. Only 1-2% of the world's population has green eyes and it is the least common eye color. Green eyes are most often found among people of Northern and Southern European origin. Countries with a high percentage of green eyes are Iceland, Sweden, Denmark, Finland, Norway, Germany, Ireland, Israel and the Netherlands[12]

Hazel

This eye shows the shift in color from light brown to green.

Some eye colors are too mixed to identify properly, and are misidentified as hazel for simplicity's sake. This subject's eye is green with brown towards the pupil.

Hazel eyes are due to a combination of a Rayleigh scattering and a moderate amount of melanin in the iris' anterior border layer.^[23][5] Hazel eyes often appear to shift in color from a light brown to a medium golden-green, and sometimes even a grayish shade. A number of studies using three-point scales have assigned "hazel" to be the medium-color between light blue and dark brown.^{[43][44][45][46][47][48][49]} This can sometimes produce a multicolored iris, i.e., an eye that is light brown near the pupil and charcoal or amber/dark green on the outer part of the iris (and vice versa) when observed in sunlight. Hazel is mostly found in some regions of the Americas, Europe, the Middle East, parts of Central Asia, parts of North India, Northern Pakistan and in Afghanistan. Rarely, hazel eyes can be found in people of sub-saharan African and East Asian descent.

Definitions of the eye color "hazel" vary: it is sometimes considered to be synonymous with light-brown, gold, or other times with green or dark green.^{[50][38][43][45][48][51][52] [53][54]} In North America, "hazel" is often used to describe eyes that appear to change color, ranging from light brown to green and even gray, depending on current lighting in the environment.

Red

'Red' eyes are also found in an extremely small percentage of the world's population, as low as 0.420%.^{citation needed} This is believed to be a result of either large quantities of the normally scarce red areas in the eye, or a small leakage of blood into the iris.^{citation needed}

The eyes of an albinistic person may appear red under certain lighting conditions due the very low quantities of melanin. "True" red eyes also exist in albinistic populations, but are very rare. ^[55]

The red-eye effect in flash photographs makes the pupils (rather than the irises) appear red. It is not related to eye color.

Violet

The appearance of "violet" eyes is thought to occur from the mixing of red and blue reflections.^[56] Some albinos have eyes that appear violet. Violet eyes are either a form of blue eyes or a mutation. ^[57]

Anomalous conditions

Aniridia

Main article: Aniridia

Aniridia: Eyes wherein the irises are not present; the eyes appear to be two large pupils.

Aniridia is a congenital condition characterized by an extremely underdeveloped iris which appears absent on superficial examination.^[58]

Ocular albinism and eye color

Normally, there is a thick layer of melanin on the back of the iris. Even people with the lightest blue eyes, with no melanin on the front of the iris at all, have dark brown coloration on the back of it, to prevent light from scattering around inside the eye. In those with milder forms of albinism, the color of the irises is typically blue, but can vary from blue to brown. In severe forms of albinism, there is no pigment on the back of the iris, and light from inside the eye can pass through the iris to the front. In these cases, the only color seen is the red from the hemoglobin of the blood in the capillaries of the iris. Such albinos have pink eyes, as do albino rabbits, mice, or any other animal with total lack of melanin. Transillumination defects can almost always be observed during an eye examination due to lack of iridial pigmentation.^[59] The ocular albino also lacks normal amounts of melanin in the retina as well, which allows more light than normal to reflect off the retina and out of the eye. Because of this, the pupillary reflex is much brighter in the albino, and this can increase the red eye effect in photographs. Edgar Winter's eyes are an example of this trait.

Heterochromia

An example of heterochromia. The subject has one brown and one hazel eye.

Main article: Heterochromia

Heterochromia (also known as a heterochromia iridis or heterochromia iridium) is an ocular condition in which one iris is a different color from the other iris (complete heterochromia), or where the part of one iris is a different color from the remainder (partial heterochromia or sectoral heterochromia). It is a result of the relative excess or lack of pigment within an iris or part of an iris, which may be inherited or acquired by disease or injury.^[60] This uncommon condition usually results due to uneven melanin content. A number of causes are responsible, including genetics such as chimerism and Waardenburg syndrome. Trauma and certain medications, such as some prostaglandin analogues can also cause increased or decreased pigmentation in one eye. On occasion, the condition of having two different colored eyes is caused by blood staining the iris after sustaining injury.

David Bowie (Jones) is a famous person often wrongly attributed with heterochromia. His apparent condition is due to a teenage injury. (One eye appears darker because the pupil is permanently dilated.) American actress Kate Bosworth has sectoral heterochromia, resulting in a hazel section at the bottom of her right blue eye, while the left is completely blue. American Actress Elizabeth Berkley has sectoral heterochromia; her right eye is half green and half brown, and her entire left eye is green. So does actor Anthony Head - he has a patch of hazel in his left eye where both eyes are blue-green overall. The lead vocalist of American band Rise Against, Tim McIlrath, has heterochromia; his left eye is blue while his right is brown. American actress Mila Kunis also has heterochromia, resulting in one blue eye and one brown-green eye. American Actress Demi Moore also has heterochromia, by having one green eye, and the other hazel.

Eye color change

Often, paler newborns have blue eyes, which change to green, hazel, light brown or dark brown. This is possibly the origin of the idiom "being blue-eyed" (i. e. naïve; gullible).

It is thought that exposure to light after birth triggers the production of melanin in the iris of the eye. By three years of age, the eyes produce and store enough melanin to indicate their natural shade. While changes in eye color of infants are more common, even in adults, eye color changes are seen, most often as a result of exposure to the sun. Sunlight triggers melanin production in the eye, as it does to the skin.

Eyedrops containing a prostaglandin analogue (such as latanoprost) may result in a permanently darkened iris; these eyedrops are commonly used to treat open-angle glaucoma.^[61]

Medical implications

Those with lighter iris color have been found to have a higher prevalence of age-related macular degeneration (ARMD) than those with darker iris color;^[47] lighter eye color is also associated with an increased risk of ARMD progression.^[62] An increased risk of uveal melanoma has been found in those with blue,green or gray iris color.^[63][13]

Eye color can also be symptomatic of disease. In particular, yellowing of the whites of the eyes is associated with jaundice and symptomatic of liver disease, including cirrhosis, hepatitis and malaria.

References

See also

• Iridology
• Hair color
• Human skin color
• Xanthophore
• List of Mendelian traits in humans

External links

Wikimedia Commons has media related to:

Eyes

• Genetics of eye color
• Eye Color and Human Diseases
• Eye colour: portals into pigmentation genes and ancestry
• Various links on human eye color