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Subject: PINEAL GLAND EVOLVED TO IMPROVE VISION, ACCORDING TO THEORY BY
NI CHD SCIENTIST


U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

National Institute of Child Health and Human Development
http://www.nichd.nih.gov

FOR IMMEDIATE RELEASE
Thursday, July 12, 2004

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Marianne Glass Miller
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PINEAL GLAND EVOLVED TO IMPROVE VISION, ACCORDING TO THEORY
BY NICHD SCIENTIST

Theory May Increase Understanding of Eye Disease, Sleep Disorders

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.

Dr. Klein explained that, in the ancestor of today's higher animals, the
conversion of serotonin to melatonin increased at night, as a way to
make vision more sensitive to low light conditions.  The conversion kept
serotonin from combining with retinaldehyde at night, when it was needed
to detect low levels of light, so that these ancestral animals could
function well under dim light.

Gradually, the early organism recognized the increase in melatonin as a
signal of nighttime and became dependent on it, according to Dr. Klein's
theory.  This signal was used to synchronize their daily cycles with the
environmental
night and day cycle.   For this signal to be reliable, the
organism needed a steady supply of serotonin in these
cells.   However, this requirement for higher levels of
serotonin conflicted with the need for greater light
detection because serotonin depleted retinaldehyde.  This conflict was
resolved by the evolution of a second photoreceptor cell, one that
housed melatonin production. The evolution of the second photoreceptor
cell allowed the original photoreceptor cell to achieve higher levels of
sensitivity to light because it was not dedicated to making high levels
of melatonin.  Eventually, the melatonin-making photoreceptors gave rise
to the pineal gland.

"To increase both sets of processes -- melatonin synthesis
and photodetection -- evolution put them into separate
cells," Dr. Klein said.  "One cell moved toward detecting light, the
other toward making melatonin."

In support of his theory, Dr. Klein noted that the photoreceptor cells
of the retina strongly resemble the cells of the pineal gland and that
the pineal cells of sub-
mammals (such as fish, frogs and birds) detect light.   In
addition, melatonin's origin in the ancestral photoreceptor cell is
indicated by the capacity of the retinas of mice, fish, frogs, and birds
to make low amounts of melatonin.

Dr. Klein points out that as humans and other primates
evolved, melatonin production was lost in the retina and
became restricted to the pineal gland.  Although melatonin
is no longer manufactured in the primate retina, AANAT
still is.  Dr. Klein suspects that the enzyme plays a role
in protecting the human retina.  Arylalkylamines
(tryptamine, phenylethylamine, and tyramine) are likely to
be made in cells of the retina, and AANAT may function to convert them
to less harmful forms.

Accordingly, AANAT may play two roles -- in the retina it
would have a detoxification role whereas in the pineal
gland it would have a role in melatonin synthesis   It's
possible, Dr. Klein said, that low levels of AANAT might
lead to the deterioration of the retina seen in macular degeneration;
and, perhaps it might be possible to prevent this disease by increasing
AANAT levels.


The NICHD is part of the National Institutes of Health
(NIH), the biomedical research arm of the federal
government. NIH is an agency of the U.S. Department of
Health and Human Services. The NICHD sponsors research on development,
before and after birth; maternal, child, and family health; reproductive
biology and population issues; and medical rehabilitation. NICHD
publications, as well as information about the Institute, are available
from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD
Information Resource Center, 1-800-370-2943; e-mail
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This NIH News Release is available online at:
http://www.nih.gov/news/pr/aug2004/nichd-12.htm

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