NEI researchers find immune cells in retina can spontaneously regenerate
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish their normal organization and function. The findings point to potential therapies for controlling inflammation and slowing progression of rare retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the most common cause of blindness among Americans 50 and older. A report on the study was published online in Science Advances. The NEI is part of the National Institutes of Health.
“Neuroinflammation is an important driver of the death of neurons in retinal diseases,” said Wai T. Wong, M.D., Ph.D., chief of the NEI Section on Neuron-Glia Interactions in Retinal Disease, and the study’s lead investigator. “Our study is foundational for understanding ways to control the immune system in the retina.” Control of the immune system is important for developing new treatments for a variety of eye conditions, including AMD, RP, or for certain types of retinal injury.
The retina is a thin layer of cells in the back of the eye that includes light-sensing photoreceptor cells and other neurons involved in transmitting visual information to the brain. Mixed in with these cells are microglia, specialized immune cells that help maintain the health of the retina and the function of retinal neurons. Microglia are also present in other parts of the central nervous system, including the brain. In a healthy retina, communication between neurons and microglia is important for maintaining the neuron’s ability to send signals to the brain. When the retina is injured, however, microglia have an additional role: They migrate quickly to the injury site to remove unhealthy or dying cells. However, they can also remove healthy cells, contributing to vision loss. Studies show that in degenerative retinal disorders like AMD and RP, inhibiting or removing microglia can help retain photoreceptors, and thus slow vision loss. But return of microglia is still important to support the retina’s neurons.
Wong and colleagues were interested in understanding what happens in the retina after microglia have been eliminated, particularly whether the cells could return to their normal arrangement and fulfill their normal functions. To test this, they depleted the microglia in the retinas of mice using the drug PLX5622 (Plexxikon), which blocks the microglial CSF-1 receptor. Microglia depend on continuous signals through this receptor for survival. Interruption of this signaling for several days caused the microglia to nearly disappear, leaving just a few cells clustered around the optic nerve — the cable-like bundle of nerve fibers that carries signals from the retina to the brain — in the mouse retinas. Since loss of microglia for a short time doesn’t affect the function of neurons, removing microglia temporarily — in order to reduce inflammation for example — could potentially be useful as a therapeutic intervention for degenerative or inflammatory disorders of the retina.
“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.”…..