Creutzfeldt-Jakob disease spreads prions throughout the eyes, researchers find

November 20, 2018

Washington, DC - November 20, 2018 - The eyes aren't only a window to the soul; they also offer a new view on rapidly-progressing neurodegenerative disorders called prion diseases.

Researchers recently studied the eyes of 11 people with sporadic Creutzfeldt-Jakob disease (sCJD), the most common and well-known prion disorder. This week in mBio, they report finding prion seeds -- the infectious proteins that cause the disease -- spread throughout the eyes of all the patients.

"It really suggests we could develop a diagnostic, eye-based assay," says pathologist and senior coauthor Christina Sigurdson at the University of California, San Diego. Future eye-based tests, she adds, may be useful to monitor disease progression and evaluate new treatments.

Prions are misfolded proteins that can emerge spontaneously in the brain; in addition, two case studies suggest they can also be transmitted through a prion-contaminated corneal transplant. About 350 people are diagnosed with CJD every year, with symptoms starting around age 60 on average, according to the National Institutes of Health. There's no treatment for CJD or other prion diseases.

When prions aggregate in the brain, they cause neurons to die. Patients with Parkinson's disease and Alzheimer's disease, similarly, are characterized by cognitive decline and an abnormal accumulation of proteins in the brain. Unlike those diseases, however, prion diseases usually accelerate rapidly, and the majority of patients die within a year of diagnosis.

Roughly 40 percent of patients with CJD develop vision or other eye problems. In some patients, vision problems are the first symptom, suggesting that prions begin accumulating in the eye or in the brain areas associated with vision at an early stage.

"We wanted to know how often prions are deposited in the eye, as well as the distribution and levels of prions in the eye," says Sigurdson.

To find out, the researchers analyzed CJD patients' eyes collected by neurologist and senior coauthor Michael Geschwind and his team at the University of California-San Francisco. Multiple eye components were sent to the laboratory of biochemist and study senior coauthor Byron Caughey, at the National Institutes of Health's Rocky Mountain Laboratory in Hamilton, Montana, for measurements using their highly sensitive prion seeding assay (RT-QuIC).

In all 11 patients, they found the highest levels of prion seeds in the retina, the tissue at the back of the eye that receives light from the lens. The assay also detected prions in other parts of the eye, including the cornea, optic nerve, lens, sclera, and muscles that help control eye movement. Previous studies using immunohistochemistry have previously found prions in patients' retinas and optic nerves, but Caughey's assay is the first to find the proteins elsewhere in the eye.

The findings suggest that surgeons who perform corneal transplants or certain eye procedures should exercise caution with their tools, says Sigurdson. "Surgeons could unknowingly contaminate their instruments with prions," she says, noting that single-use instruments may help prevent accidental spread of the disease.

The study also suggests the assay may have applications in other diseases. "If the RT-QuIC method can be used to amplify other aggregated proteins, this might lead to advances in diagnosis for Alzheimer's, Parkinson's and related diseases," says Geschwind.

Sigurdson is currently working on NIH-funded research to label prions in live mice with fluorescent dyes, with an aim toward developing a new diagnostic test. In the future, she says she wants to test the tears of CJD patients for the presence of prions, as well as further investigate the process by which prions move from cell to cell, and from brain to eye.

"Ultimately we would like to develop new treatment strategies to stop prions from spreading," she says.
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