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April 6, 2018
Digest
Immune Cells in Retina Can Regenerate

Circuits in the brain act as an internal clock that tells us it’s time to sleep, controls how long we stay asleep and, according to a new study, constantly monitors changes in external temperature and integrates that information into the neural network.
Images of mouse retina after being treated with a drug that nearly eliminates immune cells called microglia. On day 0 when the drug was stopped, nearly all microglia are gone; 7 days later, microglia have migrated across the retina, and by day 10 they have increased in number.

IMAGE: WAI T. WONG/NEI

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 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 Mar. 21 in Science Advances.

“Neuroinflammation is an important driver of the death of neurons in retinal diseases,” said the study’s lead investigator Dr. Wai Wong of NEI. “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 such as 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.

Islet Transplants Boost Quality of Life for People with Type 1 Diabetes

Quality of life for people with type 1 diabetes who had frequent severe hypoglycemia—a potentially fatal low blood glucose (blood sugar) level—improved consistently and dramatically following transplantation of insulin-producing pancreatic islets, according to findings published online Mar. 21 in Diabetes Care. The results come from a phase 3 clinical trial funded by NIAID and NIDDK.

The greatest improvements were seen in diabetes-related quality of life. Islet recipients also reported better overall health status after transplant, despite the need for lifelong treatment with immune-suppressing drugs to prevent transplant rejection. Researchers observed these improvements even among transplant recipients who still required insulin therapy to manage their diabetes.

The study was conducted by the NIH-funded Clinical Islet Transplantation Consortium.

“Although insulin therapy is life-saving, type 1 diabetes remains an extremely challenging condition to manage,” said NIAID director Dr. Anthony Fauci. “For people unable to safely control type 1 diabetes despite optimal medical management, islet transplantation offers hope for improving not only physical health but also overall quality of life.”

Pancreatic islets release the hormone insulin, which helps control blood glucose levels. In type 1 diabetes, the body’s immune system attacks and destroys the insulin-producing cells in islets.

People with the disease must take insulin to live, but insulin injections or pumps cannot control blood glucose levels as precisely as insulin released naturally from the pancreas. Even with diligent monitoring, blood glucose can often reach levels that are higher or lower than normal.

A low blood glucose level, or hypoglycemia, typically is accompanied by tremors, sweating, nausea and/or heart palpitations. These symptoms prompt the person to eat or drink to raise their blood glucose.

“People with type 1 diabetes who are at high risk for hypoglycemic events have to practice caution every moment, even while sleeping. It is an exhausting endeavor that—like the events themselves—can keep them from living full lives,” said NIDDK director Dr. Griffin Rodgers. “Although islet transplantation remains experimental, we are very encouraged by these findings, as we are by the rapid improvements in other treatments to help people with type 1 diabetes monitor and manage their blood glucose, including artificial pancreas technology.”

International Team Confirms New Genetic Mutation Link to ALS

Kinesin family member 5A (KIF5A), a gene previously linked to two rare neurodegenerative disorders, has been definitively connected to amyotrophic lateral sclerosis (ALS) by an international team from several of the world’s top ALS research labs. The findings identify how mutations in KIF5A disrupt transport of key proteins up and down long, threadlike axons that connect nerve cells between the brain and the spine, eventually leading to the neuromuscular symptoms of ALS.

The discovery, published Mar. 21 in Neuron, was led by Dr. Bryan Traynor of NIA and Dr. John Landers of the University of Massachusetts Medical School, Worcester, with key funding support from NIA, NINDS and several public and private sector organizations. Genetic data collected by teams of scientists worldwide contributed to the project.

It took a comprehensive, collaborative effort to analyze a massive amount of genetic data to pin down KIF5A as a suspect for ALS, also known as Lou Gehrig’s disease. To zero in on KIF5A, the NIH team performed a large-scale genome-wide association study, while the University of Massachusetts team concentrated on analyzing rare variants in next-generation sequence data. More than 125,000 samples were used in this study, making it by far the largest such study of ALS performed to date.

“The extraordinary teamwork that went into this study underlines the value of global, collaborative science as we seek to better understand devastating diseases like ALS,” said NIA director Dr. Richard Hodes. “These types of collaborative data collection and analysis are important in identifying the pathways underlying disease and in developing approaches to treatment and prevention.”

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