The eyes and brain work together to process the images that come into our eyes, so that we can move about and do our everyday tasks. What is going on in the brain that allows vision to take place? How do the brain and eyes work together, in particular when it comes to infants since their vision isn’t fully developed at birth. Also, is it possible to “fix” or “reboot” the eye with amblyopia, also known as “lazy eye” in adults. Two research projects at the Picower Institute at the Massachusetts Institute of Technology (MIT) shed light on the development of vision and demonstrate it is possible to “reboot” the eye with amblyopia in adults.
Development of Vision in Infants
While we have two eyes, we only see one image of something. How does vision develop in infants, so that both eyes are working together to send the images to the brain and the brain processes those images, so that the infant sees one of something. Scientists at the Picower Institute for Learning and Memory studied the vision of laboratory mice as they were developing in real time and what they learned surprised them.
Led by then graduate student Katya Tsimring and published in Nature Communications, scientists tracked spine structures of neuron dendrite branches in the visual cortex of young mice for 10 days. She saw that 40 percent of the of the branches that started the process survived past day 10. Combining the input from both eyes in order to develop binocular vision called for numerous additions and removals of the spines along the dendrites to create a set of connections.
In experiments, young mice watched black and white gratings with line of specific orientations and direction of movement that drifted across their field of view. While this was going on, scientists looked at the structure and activity of the soma or neurons’ main body and the spins along the dendrites. They tracked the structure and activity of 793 dendritic spines on 14 neurons at day 1, day 5 and day 10 of the critical vision development period.
The researchers found that 32 percent of the spines apparent on day 1 were no more on day 5. In addition, 24 percent of the spines apparent on day 5 had been added since day 1. The time span between days 5 and 10 showed similar turnover, 27 percent were eliminated, 24 percent were added. By day 10, only 40 percent of the spines seen on day 1 were there on day 10.
All of this led to the question of what allowed some spines to survive over the 10-day critical period. Earlier studies showed that the first inputs to reach binocular visual cortex neuron were from the eye on the opposite side of the head, for example the inputs from the right eye make it to the left hemisphere of the brain. These inputs influence the neuron’s soma to respond to orientation of a line, be it horizontal or diagonal. When the critical period starts, inputs from the eye on the same side of the head join the race to visual cortex neurons. This allows some of the neurons to become binocular.
As researchers gathered more data, they noticed that the spines were more likely to last if they were active and responded to the same orientation that the soma preferred. Also, spines that responded to both eyes were more active than spines that responded to one eye. That means binocular spines lasted longer than non-binocular ones.
Another thing that they noticed is that throughout the 10 days, clusters emerged along the dendrites where the neighboring spines were likely to be active at the same time. Other studies showed that by sticking together, the spines are able to combine their activity in a way that is greater than would be if they acted in isolation.
All of this means that over the course of the critical period, the neurons refined their role in binocular vision by selectively keeping inputs that reinforced their orientation preferences both by the volume of their activity and by their correlation with their neighbors. Both are necessary during the critical period to spur the turnover of the spines that are misaligned to the soma and this leads to the refinement of the binocular response.
Fixing Amblyopia in Adulthood
Amblyopia is when the brain favors one eye over the other, either due to misaligned eyes, also known as strabismus. Treatments include prescription lenses, prisms, vision therapy and eye patching. These treatments are most effective when they are done in infancy or early childhood, since the neural connections are still being formed. Scientists at the Picower Institute for Learning and Memory found that there may be a way to treat amblyopia in adults.
This work was published in Cell Reports and it showed that by temporarily anesthetizing the retina of the amblyopic eye for a couple of days, the brain’s visual response to the eye can be restored. In 2021, the lab of Picower Professor Mark Bear demonstrated that anesthetizing the retina of a non-amblyopic eye could improve vision in the amblyopic eye. Since 2021, this has been done to eyes of many species of laboratory animals. Evidence suggests that this can be done to the amblyopic eye and that is what researcher worked to find out.
Researchers wanted to know how the retina inactivation did it’s thing. One hypothesis is that blocking inputs from the retina to the neurons in the lateral geniculate nucleus (LGN) caused the neurons to fire bursts of electrical signals to downstream neurons in the visual cortex. This activity also happens in the visual system before birth and it guides early synaptic development.
This study, also done in the lab of Professor Bear, wanted to see if those bursts might play a role in potential treatments for amblyopia. First, researchers injected tetrodotoxin (TTX) to anesthetize retinas in the lab animals. They found that that the bursting occurred in the LGN neurons that received input from the anesthetized eye and in LGN neurons from the unaffected eye.
They also learned that the bursting response depended on a particular T-type channel for calcium in the LGN neurons. The good thing about this is that it gave the researchers a way to turn this off. Being able to turn it off allowed them to test whether doing so prevented TTX from having a therapeutic effect in mice with amblyopia. As it turned out, when researchers turned off the channels and disrupted the bursting, they discovered that anesthetizing the non-amblyopic eye didn’t help the amblyopic mice. That means the bursting is necessary for the treatment to be effective.
Since the bursting happens when either retina is anesthetized, researchers thought that it be help to anesthetized the amblyopic eye. So, they did an experiment where some mice that had amblyopia received TTX in the eye with amblyopia and some didn’t. The injection stopped the retina from working for two days. After a week, they measured the activity in the neurons of the visual cortex to calculate a ratio of input in each eye. They learned that the ratio was more in mice that received the treatment compared to those left untreated. This suggests that after the amblyopia eye was anesthetized, its input to the brain rose to be at par with input from the non-amblyopic eye.
“We are cautiously optimistic that these findings may lead to a new treatment approach for human amblyopia, particularly given the discovery that silencing the amblyopic eye is effective,” the scientists wrote.
The knowledge gained from these research projects increases our understanding of how binocular vision is formed and can lead to treatments that improve outcomes for adults with amblyopia. The search for answers never ends and we all benefit from the work of researchers like those at the Picower Institute.
Sources:
https://picower.mit.edu/news/connect-or-reject-extensive-rewiring-builds-binocular-vision-brain
https://www.aoa.org/healthy-eyes/eye-and-vision-conditions/amblyopia
https://picower.mit.edu/news/mit-study-shows-how-vision-can-be-rebooted-adults-amblyopia