[AI] regulating the body clock

Sanjay ilovecold at gmail.com
Thu May 22 10:57:42 EDT 2008


Regulating the Body Clock: How People with Sight Loss Sleep (From the Royal 
National Institute for the Blind's NB, © March 2008)

Because we are not conscious when we are asleep, this important aspect of 
our lives is not something we normally pay much attention to or fully 
appreciate--until,
that is, our sleep patterns are disrupted in some way.

The effects of sleep disorder are familiar and well-documented. They range 
from poor performance, loss of memory and accident-proneness to depression 
and
anxiety, and have been linked to major diseases such as Alzheimer's, heart 
disease and some forms of cancer. For night drivers, the effect may be equal
to being over the limit. For people with sight loss, poor sleep patterns 
often add to the difficulties and disorientation they are already facing. At 
best,
continuing sleep disorder can lead to a state of numbness that has been 
described as "existing rather than living."

Nor is it just a question of the amount of sleep a person has--regularity 
and timing are also important factors. Studies of shift-workers, who work at 
night
and have time to sleep during the day, have shown that both the length and 
quality of their sleep is often deficient, and that this does not alter with
time- -even after 10 or 20 years.

To understand why this is so--and why it affects the sleep patterns of many 
people with sight loss--it is necessary to understand something of circadian
rhythms (the "body clock") and the effect of the light-dark cycle.

In effect, all living organisms, from bacteria and flies to mice and men, 
have an internal clock that works to tell them to sleep or be active at the 
same
sort of period each day. The period is "circadian" or "around a day." But 
body clocks (which also regulate such things as body temperature) rarely 
correspond
exactly to the 24-hour day, and in human beings the period is slightly 
longer than 24 hours. As experiments in mine-shafts and caves have shown, 
without
the external stimulus provided by the light-dark cycle, the body clock will 
still function, but will continue to "drift" slightly--so that human beings
will get up around half an hour later every day (and mice half an hour 
earlier!).

In fact, while the body clock determines that we feel the need to sleep 
around once a day, there are two other factors that strongly drive our 
impulse to
do so. One is the effect of light and dark, causing chemical reactions that 
make us feel wakeful or sleepy, and the other is the "homeostatic" drive or
sleep debt we build up as we stay awake beyond our daily waking period.

As experiments have shown, the effects of light and dark in setting the body 
clock are particularly hard to resist. In one study of shift workers, the 
introduction
of powerful lighting in the workplace was not sufficient to counteract the 
wakefulness-inducing effects of the daylight encountered on the way home. On
the other hand, if you are "free-running" (running at the rate of your body 
clock without any external stimulus) you will have increasing problems 
sleeping
at night, and hence running on the same timing system that society demands. 
Clearly, this is a potential problem for people whose perception of light 
and
dark is reduced or totally absent, and it is well known that many people 
with sight problems do indeed experience sleep disorders.

Does this mean that people with reduced vision, or no sight at all, 
inevitably experience sleep problems, as well as the other ill-effects 
associated with
an unregulated body clock? In fact, it has been recognized for some time 
that this is not always so, and that some otherwise totally blind people 
retain
an ability to receive light information in a way that affects the circadian 
pacemaker.

Dr. Stuart Peirson of the Nuffield Laboratory of Ophthalmology, University 
of Oxford, is a member of a research group that has been looking at this 
question,
and takes up the story:

"Our group has been working on circadian rhythms for quite some time, headed 
by Professor Russell Foster. Much of our work was in basic science before we
began to look at clinical aspects, but we've now moved to Oxford and hope to 
increase our interaction with the clinical ophthalmologists at the John 
Radcliffe
hospital."

The impetus to the current research, says Dr. Peirson, was a discussion with 
clinicians at the Western Eye Hospital and City University who had been 
dealing
with a patient who had no sleep problems at all, despite having been blind 
for 40 years. "We became involved in this study because we had recently been
working on the pupillary light response (which is mediated by retinal 
photoreceptors) and a range of other non-visual responses."

A series of experiments was conducted on two patients--one in the United 
Kingdom by scientists at Imperial College, Oxford and City universities, and 
one
in the United States by study group members at Harvard and Thomas Jefferson 
universities. Despite having been blind for decades as a result of 
degenerative
retinal disease, neither reported any sleep problems, suggesting that their 
internal body clocks were still working correctly. The experiments, which 
consisted
of shining bright lights of different colors into the eyes of the patients, 
revealed that these patients retained a pupillary response to light and the
ability to influence production of the sleep hormone melatonin. Moreover, 
the study demonstrated the astonishing fact that, although they were unaware
of it, they were able to detect the presence of blue light well above the 
level of chance alone. This meant that the system--although an unconscious 
one--was
telling them at some level whether it was day or night.

Dr. Peirson explains: "As well as the rods and cones--the classic 
photoreceptors in the outer retina--there are a small percentage of the 
ganglion cells
that form the optic nerve and are also light sensitive--like a third 
photoreceptor in the eye. These cells form a kind of net across the retina."

While rods and cones have a specific image-producing function, it seems that 
these photosensitive retinal ganglion cells have a different purpose, 
performing
a number of tasks that include regulating the production of melatonin. "The 
cells express the photo pigment melanopsin," adds Dr. Peirson. "Even if you
lose all the rods and cones, the ganglion system can still be intact. And 
that is what seems to be driving these responses in patients who are 
profoundly
blind."

Around 10 percent of totally blind patients are estimated to retain their 
circadian photoreceptors in this way--although research into the phenomenon 
is
ongoing. "It may not work for everybody," says Dr. Peirson, "but there's no 
simple way of telling if you are one of those people that it could work for,
and that proportion could actually be higher.

"Without large studies it is very difficult to say. One of the things that 
we're aiming to do is work more with patients at the John Radcliffe. We'll 
be
asking them to fill in sleep questionnaires to determine whether they suffer 
from sleep disruption, and also asking them to wear wrist watches which 
monitor
activity."

Does all this offer any comfort to blind and partially sighted people who 
have sleep disorders? Dr. Peirson says that it's worth bearing in mind that 
light
could be the answer. "Your body responds to light in different ways at 
different times of the day. And so if you're exposed to light around dusk, 
it will
delay your body clock, so the next morning you'll be getting up slightly 
later. Whereas if you are exposed to light near dawn, it will push the body 
clock
in the other direction, and advance it.

"So maintaining a decent light exposure pattern is important. And one of the 
big things which is often overlooked is that indoor light is nowhere near as
bright as daylight--a bit of outdoor light does a world of good. In direct 
sunshine, the light level outside my office may be as much as 20,000 lux, 
whereas
inside, you are lucky if it is 400. Even on a grey miserable day, it is 
still almost 10 times brighter outside. So if you are exposed during your 
day,
then it tells your body clock that this is day time and synchronizes your 
system."

So, with one or two caveats--such as conditions like Stargardt's where light 
may damage the retina--it may be that bright light exposure, when that is an
option, can help set the body clock. Of course, it also depends on the type 
and level of sight loss--glaucoma, for example, can impact on the ganglion
cells. Another aspect that the researchers are highlighting is that eye 
removal, for cosmetic or other reasons, will also remove all ability to 
detect
light and may therefore lead to circadian disruption.

Another point that Dr. Peirson stresses is that for those suffering sleep 
disturbance, it is important to discuss the issues with a clinician. "The 
hormone
melatonin is sometimes administered to people with sleep disturbance.... 
Social cues will help set your body clock as well, so maintaining a good 
routine
is very beneficial."

In spite of today's 24-hour society, in which round-the-clock work, leisure 
and shopping are becoming commonplace, it seems that a return to the orderly
habits of our ancestors is the best guarantee of a good night's rest.





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