Heterochromia

Excerpt

Heterochromia or heterochromia iridum indicates a difference between the color of the two irises. It can involve the whole iris or only part of the iris (sectoral heterochromia).

It is easier to understand the determinants of iris color with the anatomy of the iris in mind. The iris and the ciliary body constitute the anterior uveal coat. The iris is composed of two anatomical layers that both contain pigment. The iris stroma is the anterior layer, consisting of loose collagenous connective tissue, the sphincter and dilator pupillae muscles, blood vessels, nerves, melanocytes, and other cells. The posterior layer (the iris pigment epithelium) consists of two layers of cuboidal epithelium. The pigment epithelium layer is derived embryologically from the anterior part of the optic cup, and hence neuroectodermal in origin. The iris stroma is mainly mesenchymal in origin. The melanocytes within the iris stroma and the ciliary body are all derived from neurocrest cells.

Another important concept is the amount, type, and location of the pigment present. A type of cell called a melanocyte produces melanin that is deposited in melanosomes. Variation in the number of melanosomes and the amount of pigment in each melanosome present in the anterior iris stroma determines eye color. The type of pigment affects eye color as well. The main two types of pigment are eumelanin (brown to black pigment) and pheomelanin (red to yellow pigment). Eumelanin is present in the iris pigment epithelium, while both eumelanin and pheomelanin are present in the iris stroma. Lipofuscin (yellow in appearance) can accumulate with age and/or ocular disease. Eumelanin is present in the iris, brain, and hair and comes in a brown and black form. Pheomelanin is present in the iris, hair, lips, nipples, glans penis, and vagina and comes in a red and yellow form. The relative presence of the different types of eumelanin and pheomelanin determines both hair and iris color. Both groups of pigment form from L-tyrosine that is converted to L-dopaquinone by tyrosinase. Tyrosinase-related protein-1, in turn, converts L-dopaquinone to eumelanin while the addition of cysteine forms pheomelanin.

Genetics plays an important role in determining eye color, with up to 150 genes involved and two genes, OCA2 and HERC2, on chromosome 15, playing a significant role. OCA2 produces "P protein," which promotes melanosome maturation, and HERC2, in turn, controls OCA2. The inheritance of iris color is largely determined by two genes as well, EYCL1 (also called the gey gene) and EYCL3 (also called the bey2 gene). The gey gene has a green and blue allele, and the bey2 gene has a brown and blue allele. The brown allele is dominant over the green allele, and both are dominant over the blue allele. Since many other genes play a role as well, this occasionally creates unexpected iris color. Congenital heterochromia can be inherited, and autosomal dominant inheritance has been reported. In many cases, however, genetic mosaicism occurs when genetic recombination or a mutation occurs during mitosis, creating an organism with genetically different cells. In albinism, both the iris stroma and the iris pigment epithelium are affected. Oculocutaneous albinism is inherited in an autosomal recessive manner and caused by mutations in tyrosinase, tyrosinase-related protein-1, and OCA2. Ocular albinism is inherited in a sex-linked recessive manner.

Eye color changes from lighter tints to darker during the first year of life, with most changes occurring between 3 and 6 months of age. These changes are dependent on adrenergic innervation. Horner syndrome's lack of adrenergic innervation causes a lighter-colored iris that will have a smaller pupil in dark conditions.

Other structures within the iris and elsewhere may affect the color of the iris as well. First, iris atrophy from conditions such as pigment dispersion syndrome as well as an iridocorneal endothelial syndrome, and iris damage such as caused by surgery or injury can cause heterochromia. Second, anisocoria (different pupil size), which can result from ocular trauma, Adie's pupil, or Horner syndrome, or an abnormal pupil such as is the case with iris coloboma, can create the impression of heterochromia. Neoplastic or hamartomas structures within the iris such as iris naevi and Lisch nodules can cause heterochromia as well. Finally, asymmetrical corneal changes such as band keratopathy, scarring, or edema can create the impression of heterochromia.

Finally, several optical phenomena and light conditions can affect the appearance of the iris. For example, reduced ambient light can cause an amber eye to appear brown. Selective absorption and reflection of other (non-pigment) molecules such as hemoglobin and collagen describe most of the variations in eye color that are not attributed to pigmentation of the iris. However, Rayleigh (causing the blue appearance of the sky) and Tyndall scattering, as well as diffraction, can contribute to eye color as well. Raman scattering and constructive interference (responsible for the coloration of bird and butterfly feathers and brightly colored irises of many animals) do not play a role in human iris coloration.

In addition to the color, human iris tissue may form complex patterns with distinct features. These distinct features can be used for automatic personal identification like fingerprints.