Indian-origin researcher's study may help develop pills for body clock related conditions

Washington, June 11 : Symptoms associated with jet lag, shifts in work schedules, seasonal changes in day lengths, and disorders like insomnia and depression may become treatable with a pill if an Indian-origin researcher at the Salk Institute for Biological Studies has his way.

Dr. Satchidananda Panda says that this objective may be accomplished by understanding how the elimination of melanopsin, a photopigment in the eyes that measures the intensity of incoming light, makes the body clock blind to light without having any adverse effect on normal vision.

"It is entirely possible that in many older people a loss of this light sensor is not associated with a loss of vision, but instead may lead to difficulty falling asleep at the right time," says Dr. Panda, an assistant professor in the Regulatory Biology Laboratory.

In an article in the journal PLoS ONE, Dr. Panda highlights how melanopsin is different from two types of light-sensitive detectors in the retina, known as rod and cone cells.

"It functions like a light meter in a camera, but does more than set our biological clock. The incoming information about light intensity is also used to adjust the aperture or pupil size, regulate melatonin synthesis and physical activity," says Dr. Panda.

He says that unlike the millions of rod and cone cells imparting vision, melanopsin is only present in roughly 2,000 cells, which are known as melanopsin-expressing retinal ganglion cells (mRGCs).

He has revealed that the such cells are embedded in the inner retina, and that they signal directly to the human circadian clock-a cluster of cells less than half the size of a pencil eraser, which sits just above the point where the optic nerves cross.

It is through these signals that the clock synchronizes the body's daily rhythms with the rising and setting of the sun, thereby telling the body when it's time to go to sleep, when to be hungry, and when to wake up.

The circadian clock is also responsible for making people feel completely out of sync when they cross several time zones.

Dr. Panda points out that blind mice without functional rods and cones can still use mRGCs to adjust their biological clock, the aperture of their pupils and light-dependent activity-collectively known as non-image forming visual responses.

However, mice without melanopsin do not become completely blind to light, he adds.

Dr. Megumi Hatori, first author of the study, says that she used the technique of genetic engineering while experimenting on mice, and rendered their mRGCs susceptible to diptheria toxin.

She says that she exploited the toxin to kill melanopsin-expressing cells of eight weeks old mice.

"We found that killing the melanopsin-expressing cells makes the mouse circadian clock completely blind to light, but these mice can still perform normal image-forming visual tasks perfectly fine," says Dr. Megumi.

Dr. Panda adds: "Since all the information passes through mRGCs, these cells have emerged as a unique cellular target for therapeutic intervention in circadian clock related disorders."

He says that he has already started screening small molecules for their ability to tweak melanopsin's light sensing properties, and thereby slowing down or enhancing the resetting of our biological clock.

ANI