Scientists at the University of California, Berkeley, have revealed that the light-sensitive cells in the developing retinas of babies in the womb interact with each other in an interconnected network. This discovery has shown that the retina is offered more light sensitivity than previously thought, meaning babies in the womb can actually see more than we think.
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Ganglion cells are a type of neuron found in the ganglion cell layer in the retina, and receive visual information from bipolar cells and retina amacrine cells, and send messages through the optic nerve to the brain. These cells begin to develop between weeks five and 18 of pregnancy.
Around three percent of these ganglion cells are light-sensitive, and scientists are currently aware of six different subtypes of ganglion cells that communicate with different parts of the brain, with some regulating the body’s circadian rhythms, and others helping our pupils constrict when facing intense light. Other subtypes have even been found to influence mood and emotions.
In studies on mice and monkeys, it has been found that ganglion cells communicate with one another through gap junctions, the specialized intercellular connections between a huge number of cell types. These junctions allow electrical impulses (along with molecules and ions) to pass through ‘gates’ between cells.
The study explains that gap junctions are able to influence light responses in the developing retina in several ways.
“First, gap junction coupling enhances light sensitivity across the population of ipRGCs. Second, gap junctions conduct light-evoked currents from ipRGCs to cells that lack intrinsic phototransduction. Third, gap junction networks exhibit plasticity that regulates the light sensitivity of ipRGCs.”
The results found in these animal studies suggest that the developing eye is far more complex than scientists previously thought.
Marla Feller is a UC Berkeley professor of molecular and cell biology and the Paul Licht Distinguished Professor in Biological Sciences and a member of UC Berkeley’s Helen Wills Neuroscience Institute. She was the senior author of the paper detailing research into embryonic retinal development titled “Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina” published in Current Biology in November 2019.
Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they play a role in how the retina connects up to the brain,”
Senior author Marla Feller, UC Berkley
"Maybe not for visual circuits, but for non-vision behaviors. Not only the pupillary light reflect and circadian rhythms, but possibly explaining problems like light-induced migraines, or why light therapy works for depression.”
Feller and her mentor, Carla Shatz of Stanford University, were major parts of research showing that ‘retinal waves’, the spontaneous electrical activity in the eye during in utero development, are essential for creating the brain networks that process images later in life. The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs) were only discovered ten years ago.
Feller explained how this discovery after 20 years of studying the developing retina surprised scientists at the time.
“We thought [mouse pups and the human fetus] were blind at this point in development. We thought that the ganglion cells were there in the developing eye, that they are connected to the brain, but that they were not really connected to much of the rest of the retina, at that point. Now, it turns out they are connected to each other, which was a surprising thing.”
A UC Berkeley graduate student Franklin Caval-Holme used two-photon calcium imaging, whole-cell electrical recording, pharmacology, and anatomical techniques to show that the six subtypes of ipRGCs were electrically linked through gap junctions in the retinas of newborn mice. Caval-Holme found that there was a retinal network that detected light and even responded to the light’s intensity.
However, gap junction circuits were not essential to every ipRGC subtype. This provided a way in which scientists could possibly work out which subtypes facilitate the non-visual behaviors induced by light.
Caval-Holme expanded on the scope for new research in this area.
“Aversion to light, which [mouse] pups develop very early, is intensity-dependent,” Caval-Holme said. “We don’t know which of these ipRGC subtypes in the neonatal retina actually contributes to the behaviour, so it will be very interesting to see what role all these different subtypes have.”
This research also unearthed evidence suggesting that these gap junction circuits are able to ‘tune’ themselves in order to adapt to different light intensities, which Feller believes may have an important developmental role.
“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/off response, where you need some light or no light,” Feller 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.”
Caval-Hole, F. et al. (2019). Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina. Current Biology. DOI: https://doi.org/10.1016/j.cub.2019.10.025