A new study from the National Eye Institute has found that immune cells known as microglia can completely repopulate themselves in the retina after being nearly demolished. The work was published yesterday in Science Advances.
"Neuroinflammation is an important driver of the death of neurons in retinal diseases," said Wai T. Wong, M.D., Ph.D. "Our study is foundational for understanding ways to control the immune system in the retina."
In the retina, communication between neurons and microglia is important for maintaining the neuron's ability to send signals to the brain. However, when the microglia is damaged, they migrate to the injury site to remove defective cells but then also remove healthy cells, contributing to vision loss.
Wong and colleagues were interested in understanding what happens in the retina after microglia have been eliminated to see if the cells would return to their normal functions. Using a drug called, PLX5622 (Plexxikon), they were able to block the microglial CSF-1 receptor. Without being able to signal to CSF-1, the microglia began to disappear as they depend on that signaling to survive. The group believes that loss of the microglia for a short time could help reduce the inflammation in the retina since neurons don't need them to function.
"If we were to get rid of the microglia while a large, inappropriate immune response was happening," said Wong, "we might be able to miss the worst of the inflammation, but still come back into balance at a later point in time. We could hit pause on the immune system in the retina in a directed way."
When the team stopped administering Plexxikon to the animals, they found that within 30 days the microglia started to return and after 150 days, they were at normal density.
"The organization of these immune cells is quite elaborate, and all the organization comes right back," Wong said. "We can actually image the eye and watch these cells divide and split and migrate as part of the repopulation response."
However, the researchers want to check if the newly returned microglia were fully functional. So they used an injury model where photoreceptor cells are damaged by bright light and found that the microglia were able to activate and migrate to the injury site as they did before. They also found that the microglia were able to communicate with and maintain the function of neurons in the retina, especially when the depletion was short-lived.
The findings from this study could hopefully help with the development of new treatments for various eye conditions such as age-related macular degeneration or retinitis pigmentosa.
Image: Microglia in a healthy adult mouse retina. Image courtesy of Wai T. Wong at the National Eye Institute.