Immune cells in the 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).

Microglia in a healthy adult mouse retina. Image credit: Wai T. Wong/National Eye Institute

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.

The scientists depleted the microglia in the retinas of mice using the drug PLX5622, 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.

Within 30 days after stopping the drug, they found that the microglia had repopulated the retina, returning to normal density after 150 days. Using a novel method for visually tracking microglial movements in the retina, they determined that the returning microglia initially grew in clusters near where the optic nerve leaves the eye.

Gradually, new microglia expanded outwards towards the edges of the retina. Over time, the cells re-established an even distribution across and through the various layers of the retina.

The researcher found that the microglia were able to communicate with and fully maintain the function of neurons in the retina, especially when the depletion was short-lived. (National Institutes of Health)

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