The pineal gland - which regulates the cycles of sleep and waking - appears to have evolved as an indirect way to improve vision, by keeping toxic compounds away from the eye, according to a new theory by a researcher at the National Institute of Child Health and Human Development at the National Institutes of Health.
The theory has implications for understanding macular degeneration, a condition causing vision loss in people age 60 and older.
The theory is described in the August Journal of Biological Rhythms and represents the work of David Klein, Ph.D., Chief of NICHD's Section on Neuroendocrinology. Dr. Klein studies melatonin, the pineal hormone that regulates sleep and wake cycles.
"Dr. Klein's theory extends our understanding of the pineal gland as a factor controlling the body's daily rhythms," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development. "Klein's new theory reminds us of the common evolutionary origin of cells in the pineal gland and retina and forces us to look at one of the enzymes used to make melatonin from a new perspective - as a detoxifying system in the retina."
Briefly, the theory holds that melatonin was at first a kind of cellular garbage, a by-product created in cells of the eye when normally toxic substances were rendered harmless. Roughly 500 million years ago, however, the ancestors of today's animals became dependent on melatonin as a signal of darkness. As the need for greater quantities of melatonin grew, the pineal gland developed as a structure separate from the eyes, to keep the toxic substances needed to make melatonin away from sensitive eye tissue.
For sight to be possible, Dr. Klein explained, a form of vitamin A (also called retinaldehyde) must chemically attach itself to rhodopsin, a protein found in the light detecting cells of the retina (the photoreceptors). When struck by light, the retinaldehyde-rhodopsin combination undergoes physical changes that begin a series of chemical reactions. These reactions ultimately generate an electrical signal that travels into the brain, making vision possible.
This is a one-time event for each retinal-rhodopsin combination. In the process, light also renders the retinaldehyde inactive and frees it from rhodopsin. The free, inactive retinaldehyde is then recycled within the retina to an active form, so that it can again participate in light detection.
However, a problem arises during this recycling process: When retinaldehyde is not attached to rhodopsin, it can combine with substances known as arylalkylamines. Klein has found that one molecule of an arylalkylamine can combine with two molecules of retinaldehyde to form a substance known as a bis-retinal arylalkylamine. After this occurs, the retinaldehyde molecule can no longer be used to detect light, Dr. Klein said. Arylalkylamines are potentially dangerous because they can damage many chemicals in the cell. Some arylalkylamines are generated naturally. These include tyramine, tryptamine, phenylethylamine, and serotonin. In addition, Dr. Klein theorizes that other toxic arylalkyamines were also present in the environment early in evolution.
Roughly 500 million years ago, animals acquired the ability to make an enzyme known as arylalkylamine N-acetyltransferase (AANAT). Earlier this year, Dr. Klein and his colleagues presented evidence that animal cells may have acquired this ability by incorporating bacterial DNA into their own DNA. A release describing the earlier finding appears at http://www.nichd.nih.gov/new/releases/genes.cfm.
AANAT chemically alters arylalkylamines to prevent them from combining with retinaldehyde. AANAT alters serotonin by changing it to a compound known as N-acetylserotonin. However, N-acetylserotonin is still toxic to the cells of the retina, although less so than is serotonin. A second enzyme, hydroxyindole-O-methyltransferase (HIOMT) further changed N-acetylserotonin, converting it into melatonin, which is relatively harmless to the eye. In the earlier paper, Dr. Klein and his coworkers also provided evidence that, like AANAT, HIOMT originated in bacteria. He believes that these enzymes - both of which are essential for melatonin synthesis - were acquired by the ancestral eye to increase sensitivity to light. The enzymes presumably were acquired before the evolution of the pineal gland.