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January 12, 2018
FOCUS OF AMD RESEARCH
Microglia Are the Eye’s Electrician

Cells in our eyes called microglia function as a kind of maintenance electrician. They move their fine processes in the retina—the light-sensitive tissue at the back of the eye—constantly assessing the retina’s synaptic connections to make sure they are in good working order. So said Dr. Wai Wong, head of NEI’s unit on neuron-glia interactions in retinal disease, at the 10th Sayer Vision Research Lecture recently.

On hand at the lecture are (from l) Dr. Paul Sieving, NEI director; Dr. Jane Sayer, a research scientist at NIDDK who established the lecture series in honor of her parents, Winthrop and Laura Sayer; and Dr. Wai Wong.
On hand at the lecture are (from l) Dr. Paul Sieving, NEI director; Dr. Jane Sayer, a research scientist at NIDDK who established the lecture series in honor of her parents, Winthrop and Laura Sayer; and Dr. Wai Wong.

Since the discovery of microglia as resident macrophage cells of our central nervous system more than 100 years ago, scientists have wondered how they might play a role in neurodegenerative diseases in the brain and the retina. Wong described his team’s work examining how microglia can contribute to the maintenance of a healthy retina, as well as how they go awry during aging and in the context of degeneration.

Specifically, Wong’s research focuses on how microglia contribute to retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa. These diseases are important causes of irreversible blindness in the United States, with multiple forms of these conditions still without effective treatment.

In a healthy retina, microglia contribute to the normal functioning of the connections between nerve cells called synapses, Wong explained. The motility of fine microglial processes, as well as their spatial coverage of the retina, enables frequent contact between microglia and synapses, facilitating constant communication and interaction. Evidence shows that microglia actively maintain the function and structural integrity of these connections, enabling the retina’s physiological response to light.

Microglia (green) shown in a mouse retina
Microglia (green) shown in a mouse retina

The lab’s studies of mice and primates found that microglial structure and distribution are not static with aging but change progressively. Microglia become more numerous, but individually they are smaller and less branched in structure and demonstrate decreased motility in their processes, suggesting decreasing function with age.

Microglia also change in their response to focal injury as they grow older. Following focal retinal injury, microglia mobilize to the injury site but with aging, they were slower to respond immediately after injury. They also lingered long-term, suggesting that age may predispose them to being part of a maladaptive chronic inflammatory response.

“We also see age-related changes in the distribution of microglia within the retina,” Wong said. In young mice, microglia are confined to the inner retina. As the retina ages, microglia start venturing into the outer retina to accumulate in the sub-retinal space. Studies suggest that microglia in the outer retina become transformed in a way that predisposes the retina to inflammatory diseases.

Wong and his colleagues at NEI are studying the drivers that cause the microglia to age. Understanding those factors may help inform efforts to control or even reverse microglia-related chronic inflammation as a potential treatment strategy for AMD. It’s possible that microglia themselves may become a cellular target for therapy.

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