Retina’s Biological Clock Shows Independence From the Brain

Published Online September 15, 2015
Proceedings of the National Academy of Sciences

The retina, the light-sensitive inner layer of the eye, always knows what time is it. The enduring question has been: How?

That question led to a light-bulb moment for researchers, who determined that the retina’s own biological clock functions independently from the one in the brain.

They also found that the retinal clock uses daylight as a time-setting signal, a process called photoentrainment.

“In other words,” says Richard Lang, PhD, “as long as the retina continues to receive daily light stimulation, it will maintain time.”

In the multi-institutional study, published in Proceedings of the National Academy of Sciences, researchers made a second significant finding. They revealed that this light-dependent time-setting mechanism uses a new opsin molecule called neuropsin as a light detector.

Lang directs the Visual Systems Group and the Center for Chronobiology at Cincinnati Children’s. Other investigators included Shruti Vemaraju, PhD, and Minh-Thanh Nguyen, PhD.

In mammals, behavioral circadian rhythms are synchronized to light and dark cycles through rods, cones, and photosensitive cells in the retina.

These molecular circadian rhythms in the retina are themselves synchronized to light and dark signals, but the study was the first to show how this photoentrainment, in an ex vivo setting, requires neuropsin.

“Remarkably,” researchers wrote, “the circadian clocks in the cornea are also photoentrained ex vivo in an OPN5-dependent manner.”

Many tissues in the body have their own biological clocks. But this study suggests that these tissues may function independently of the brain’s biological clock, located in the suprachiasmatic nucleus.

“We are investigating this possibility,” Lang says.

Fig A:  Neuropsin expression in ganglion cells of the mouse retina:  In these images, the expression of the Neuropsin gene (Opn5) is indicated by the blue labeling. Panel A is a control retina that does not contain the Opn5lacz reporter gene and so no blue labeling is apparent. Panels B and C show retina, labeled for Opn5lacz expression and showing the retinal ganglion cells that express Neuropsin. Panel D shows, in a section through the labeled retina, that Neuropsin expressing cells reside in the innermost layer of the retina.
Click image to view caption.

Citation

Buhr ED, Yue WW, Ren X, Jiang Z, Liao HW, Mei X, Vemaraju S, Nguyen MT, Reed RR, Lang RA, Yau KW, Van Gelder RN. Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea. Proc Natl Acad Sci U. S. A. 2015 Oct 20;112(42):13093-8.

A photo of Richard Lang.

Richard Lang, PhD

A photo of Shruti Vemaraju, PhD.

Shruti Vemaraju, PhD