May 2019

NEWS

Research Highlight
On alert for prions in the eye


by Maxine Lipner EyeWorld Senior Contributing Writer

While Creutzfeldt-Jakob disease (CJD) is a neurologic condition, new study results1 indicate that levels of prions associated with it can be found in the eye, according to Michael Geschwind, MD, PhD. “The levels in the retina in some cases were at the same concentration as those in the brain,” he said. With the most common forms of the degenerative condition, patients experience rapidly progressive dementia, problems with coordination, myoclonus, and death within a few months from onset.
CJD can occur spontaneously, be genetic, or be acquired. “About 15% is due to a mutation of the prion protein gene,” Dr. Geschwind said, explaining that this alteration causes the protein made by the prion protein gene to be more susceptible to misfolding.
About 85% of cases are spontaneous, but the disease can rarely be acquired from medical procedures, as well as eating beef contaminated by bovine spongiform encephalopathy. “There have been some cases in which physicians would implant depth electrodes into the brain prior to epilepsy surgery, then clean and sterilize the wires in a way that would destroy the viruses and bacteria, but not the misfolded protein,” Dr. Geschwind said. In at least two cases, CJD has been transmitted by corneal transplantation.

Studying CJD

Due to the eye’s connection with the brain through the optic nerve, investigators hypothesized that if prions were in the brain, they could be in the optic nerve and other ocular structures as well, Dr. Geschwind said.
An earlier study of his, as well as research of others, indicated a connection between CJD and visual symptoms.2 “When we examined the first symptom in about 100 cases of prion disease, we found that just under 10% were visual,” he said, adding that often the first symptoms CJD patients report are visual changes such as double vision or clouding. Patients may be in their mid- to late 60s, which is not only a peak age for spontaneous CJD but also when cataracts tend to occur. “Patients often undergo ophthalmic procedures, thinking that’s the reason for their visual trouble, but it turns out this was actually coming from their brain and not their eyes,” Dr. Geschwind said.
To detect whether there were prions in ocular structures, investigators employed a new method called RT-QuIC, which was developed by the lab of Byron Caughey, PhD. “It’s a way of detecting prions by multiplying them,” Dr. Geschwind said.
Using the RT-QuIC method, they identified prions in all ocular structures they evaluated, with the highest levels in the retina. “What we have not shown is whether or not the prions are transmissible,” he said. “But the fact that the retina is at as high a level as the brain, and we know the brain can be transmissible, our conclusion would be if touching the retina, we should treat equipment the same way we would when treating the brain.”

Safety measures

When dealing with potential prion cases, Dr. Geschwind’s hospital, the University of California, San Francisco Medical Center, uses only essential people in the OR and sequesters the equipment until a CJD diagnosis is made. If positive for CJD, the equipment is disposed of. Otherwise it is sterilized and put back in circulation, he said.
If CJD is suspected, a neurological history may show other things besides visual symptoms, Dr. Geschwind said. A brain MRI in conjunction with an evaluation by an experienced physician could determine this.
“In the future, we are interested in knowing if by performing the RT-QuIC test on tears or scrapings from a suspect eye we could screen for CJD,” Dr. Geschwind said. Dr. Geschwind’s collaborators, Amydis and Dr. Christina Sigurdson at the University of California, San Diego, have been researching a fluorescent, prion-binding compound that could be a detection tool as well. Knowing CJD status preoperatively would allow for safer surgery and protection-control protocols, he concluded.

About the doctor

Michael Geschwind, MD, PhD
Michael J. Homer Chair in Neurology
University of California, San Francisco

References

1. Orru CD, et al. Prion seeds distribute throughout the
eyes of sporadic Creutzfeldt-
Jakob disease patients. MBio. 2018;9:e02095–18.
2. Rabinovici GD, et al. First symptom in sporadic Creutzfeldt-Jakob disease. Neurology. 2006;66:286–7.

Financial interests

Geschwind: National Institute of Aging/National Institutes of Health, Alliance BioSecure

Contact information

Geschwind: Michael.Geschwind@ucsf.edu


 

On alert for prions in the eye On alert for prions in the eye
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