Learn how fetuses respond to light exposure in the womb, and what this reveals about early visual development and potential light therapy applications.
By the second trimester, long before a baby's eyes can see images, they can detect light.
Until now, the light-sensitive cells in the developing retina—the thin sheet of brain-like tissue at the back of the eye—were thought to be simple on-off switches, presumably there to set up the 24-hour, day-night rhythms parents hope their baby will follow. University of California, Berkeley, scientists have now found evidence that these simple cells actually talk to one another as part of an interconnected network that gives the retina more light sensitivity than once thought and that may enhance the influence of light on behavior and brain development in previously unsuspected ways.
In the developing eye, roughly 3% of ganglion cells—the retina cells that send messages through the optic nerve into the brain—are sensitive to light. To date, researchers have identified about six different subtypes that communicate with various brain regions. Some talk to the suprachiasmatic nucleus to tune the internal clock to the day-night cycle. Others send signals to the area that makes pupils constrict in bright light.
Yet others connect to more surprising areas: the perihabenula, which helps regulate mood, and the amygdala, which processes emotions.
Recent evidence from mice and monkeys shows that these ganglion cells also communicate with one another through electrical connections called gap junctions, suggesting more complexity in the immature rodent and primate eye than previously imagined.
"Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they help shape how the retina connects to the brain," said Marla Feller, a UC Berkeley professor of molecular and cell biology and senior author of a paper published this month in the journal Current Biology. "Perhaps not for visual circuits, but for non-vision behaviors—not only the pupillary light reflex and circadian rhythms, but possibly explaining problems like light-induced migraines or why light therapy can ease depression."
Parallel systems in the developing retina
The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs), were discovered only about 10 years ago, surprising researchers like Feller, who had studied the developing retina for nearly two decades. She and her mentor, Carla Shatz of Stanford University, showed that spontaneous electrical activity in the eye during development—so-called retinal waves—is critical for setting up the correct brain networks to process images later on.
That finding led to her interest in whether ipRGCs might function in parallel with spontaneous retinal waves in the developing retina.
We thought the pups—and by extension the human fetus—were blind at this stage. We believed the ganglion cells were present and connected to the brain, but not yet linked to the rest of the retina. Now it appears they are connected to one another, which was a surprise.
Marla Feller, the Paul Licht Distinguished Professor in Biological Sciences and a member of UC Berkeley's Helen Wills Neuroscience Institute.
UC Berkeley graduate student Franklin Caval-Holme combined two-photon calcium imaging, whole-cell electrical recording, pharmacology, and anatomical techniques to show that the six types of ipRGCs in the newborn mouse retina link up electrically via gap junctions, forming a network that not only detects light but also responds to its intensity, which can vary nearly a billionfold.
Gap-junction circuits proved critical for light sensitivity in some ipRGC subtypes but not in others, offering a potential way to identify which subtypes drive specific non-visual behaviors evoked by light.
"Aversion to light, which pups develop very early, is intensity-dependent," suggesting that these neural circuits could be involved in light-aversion behavior, Caval-Holme said. "We don't know which of these ipRGC subtypes in the neonatal retina actually contributes to the behavior, so it will be fascinating to see what role all these different subtypes have."
The researchers also found evidence that the circuit tunes itself in a way that could adapt to the intensity of light, which probably has an important role in development, Feller said.
"In the past, people demonstrated that these light-sensitive cells are important for things like the development of the blood vessels in the retina and light entrainment of circadian rhythms, but those were kind of a light on/light off response, where you need some light or no light," she said. "This seems to argue that they are actually trying to code for many different intensities of light, encoding much more information than people had previously thought."
University of California, Berkeley
Caval-Holme, F., et al. (2019) Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina. Current Biology. doi.org/10.1016/j.cub.2019.10.025.
Further reading: NIH Child Health
