Re: What can cause a change in eye color during adolescence?

Hi Melissa!

Thanks for your question! I must admit that I had fun doing some research for your question. Your question seems to address eye color and what might cause eye color to change later in life. In my answer, I will focus on what exactly is responsible for producing eye color and what might be responsible for changes in color. I will not discuss in detail what is known regarding the genetics of eye color in humans. This topic has been addressed in a previous MadScientist question.

Basic structure of the human eye
First, I think it is important to briefly review some of the relevant anatomy of the human eye. The cornea is located at the front of the eye and is the transparent window through which light first passes before traveling through an opening called the pupil. The iris appears as the colored part of the eye and is responsible for regulating the size of the pupil, which in turn influences the amount of light that enters the eye. Finally, at the back of the eye lies the retina, a multilayered structure consisting of a diverse array of cell types, which receives visual stimuli from the environment and transmits this information to the brain, via the optic nerve for further processing.

The iris
The iris (plural: irides) gets its name from Iris, the Greek goddess of the rainbow and messenger of the gods. Structurally, the iris contains two different layers. The innermost layer (closest to the back of the eye) is called the iris pigment epithelium, or IPE for short. The cells of this layer appear as tiny cubes and are stacked in a compact and orderly arrangement, much like bricks. Furthermore, as the name suggests, these cells appear pigmented. The top layer is referred to as the iris stroma, which consists of less orderly and more loosely arranged cells. There are several different cell types present in the stroma, including a specialized population of pigmented cells called melanocytes. Melanocytes are cells that synthesize pigment (referred to as melanin) and originate from an embryonic structure called the neural crest.

Structural elements that determine iridial color
There are three main factors relating to iridial structure that may influence its color: (1) the pigment in the IPE, (2) the pigment content of the iris stroma, and (3) the cellular density of the iris stroma. From the paragraph above, we know that there are two regions in the iris that contain pigment, or melanin: one is in the IPE, which I have already eluded to, and the other is in the iris stroma. For the most part, the amount and distribution of melanin in the IPE is similar in irides of different colors. Therefore, it is unlikely that the IPE itself is a major determinant of iris color. However, it seems that the melanocytes in the iris stroma do play a role. These pigmented cells store their melanin in specialized organelles called melanosomes. It is currently held that much of the variation in iris color can be attributed to variation in the number and size of melanosomes within these melanocytes. In contrast, it seems that the actual number of melanocytes remains relatively constant between irides of different colors. Thus, the amount and distribution of melanin contained within the melanocytes themselves is thought to be a major determinant of eye color. The cellular density of the iris stroma plays a relatively minor role in iridial color. Light of longer wavelengths (red light, for example) readily penetrates the iris and is absorbed. However, some shorter wavelengths, primarily blue light, is reflected back and scattered by the iris stroma. This means that irides with little or no pigment in the iris stroma appear blue due to the reflection and scattering of blue light.

Blue, Green and Brown
So, how do these various structural elements translate into the different iridial colors that we see? Well, we have already talked a little about what causes blue eyes. Essentially, these individuals have very few melanosomes in the iris stromal melanocytes, and the resulting blue color is due to light reflection and scattering. I should emphasize that blue-eyed individuals do not lack all pigment in their eyes-they have normal melanin content in the IPE but relatively little melanin in the iris stroma. (NOTE: Individuals who are completely deficient in melanin have red eyes. This condition is called albinism and is due to a genetic mutation in one of the enzymes responsible for the synthesis of melanin. The eyes appear red due to the "unmasking" of the blood contained in the vessels of the eye in the absence of melanin.) Brown irides result from a high melanin content in the iris stroma-that is, a large number of melanosomes contained within the melanocytes. Green or hazel irides are the product of a moderate amount of melanosomes. Therefore, in a basic sense, there is a spectrum of iridial color ranging from blue to green to brown that results from a continuum of increasing melanosome number.

Changing eye color
Under normal physiological conditions, exactly what might cause gradual changes in eye color beyond adolescence is not known. Presumably, environmental and/or genetic factors might interact with the cells in the iris, causing an increase or decrease in the degradation of melanin within the stromal melanocytes, and perhaps a change in the number and/or size of these melanocytes. It is possible that stress may impact this process, but there is no evidence to support that claim per se. I came across one interesting observation that may be relevant here. A medication called latanoprost causes an increase in iris pigment in some patients. This drug is a prostaglandin analogue, which means that it mimics this particular hormone in the body. Exactly how it does this isn't clear. But, this may provide some evidence that various hormones in the body can alter iridial pigmentation over time.

An interesting side note here is the observation that many infants have eyes that appear blue at birth, but which later change color. This change primarily reflects an initial delay in melanin production within the iris stromal melanocytes, with full pigmentation achieved by around three years after birth.

I should also mention that there are a few diseases that are known to result in a progressive loss of iris color (Horner's syndrome and Fuchs' heterochromic iridocyclitis are two examples). I share this information only as a point of interest and it is by no means a diagnosis. (I am not a physician so please seek professional advice if you suspect that you have a medical problem.)

I hope this information is helpful! Please feel free to contact me if anything I have discussed is unclear. I have listed a few references below.

-Nikki
nmdavis@fas.harvard.edu

References
There is primarily one journal article that I used for much of this information. It is unfortunate that the details of what governs differences in eye color are often not discussed. The reference for the article is listed below. If you are interested and unable to locate it, let me know and I can send you a copy.

Imesch PD, Wallow IHL, Albert DM. "The Color of the Human Eye: A Review of Morphologic Correlates and of Some Conditions that Affect Iridial Pigmentation." Survey of Ophthalmology Volume 41, Supplement 2 pp. S117-S123, February 1997.

Also, a useful general reference on the eye is:

The Eye: Basic Sciences in Practice Forrester, JV et al. 1996, WB Saunders Company