A recent study in rats has revealed that production of the hormone vasopressin in the eye helps to program the brain’s biological clock.
The research, led by Mike Ludwig, PhD, at the University of Edinburgh, added to previous findings that retinal ganglion cells (RGCs) are responsible for communicating information on outside light intensity to the brain.
According to the paper, which was published in The Journal of Physiology, scientists have already established that an area within the hypothalamus called the suprachiasmatic nucleus (SCN) moderates circadian rhythms based on cues from ambient light perceived by the eye. For example, bright morning light synchronizes the 24-hour cycle, telling us it is time to wake up and be alert. This explains why looking at a bright screen at night may interfere with our internal clock and cause sleeplessness.
Until now, however, it was not known exactly how the RGCs relay the information to the SCN. Cells in the SCN use vasopressin to modulate or “entrain” circadian rhythm-driven processes within the brain, and it was assumed that the role of the hormone was limited to these functions.
A series of experiments by the Edinburgh team demonstrated instead that retinal cells express vasopressin, thought before to be synthesized only in the hypothalamus, in response to light, and they use it to signal the SCN.
First, the researchers showed that a bright pulse of light excited the RGCs in the rat eye, causing them to release vasopressin. Next, they showed that neurons in the SCN were also activated after a pulse of light. But when a vasopressin-inhibiting compound was injected into this brain region, the SCN cells responded less to the same pulse of light.
Interestingly, the team also found that SCN stimulation induced a phase shift in the rest-activity cycle via enhanced expression of the transcription factor c-Fos, but only if the rats had been subjected to a period of darkness prior to light stimulation. When the rats were exposed to light in the beginning of a dark phase, their SCNs did not show levels of c-Fos adequate to reset the circadian rhythm. This suggests that the brain resists letting the cycle reset to “morning” unless a period of darkness, or “night,” has been observed.
Though the findings have yet to be confirmed in humans, Ludwig believes the vasopressin pathway holds promise for drug development.
"Our exciting results show a potentially new pharmacological route to manipulate our internal biological clocks,” he said. “Studies in the future which alter vasopressin signaling through the eye could lead to developing eye drops to get rid of jet lag, but we are still a long way off from this."