Prion disease can be transmitted through eye surgery

Researchers in the United States have found evidence of the infectious agent that causes sporadic Creutzfeldt-Jakob disease (sCJD) in the eyes of deceased patients. The discovery could lead to the development of tests for the early diagnosis of the disease, which is caused by abnormal forms of normally harmless prion proteins, but also suggests that the disease could be transmitted through procedures such as corneal transplants.

“Almost half of patients with CJD develop visual disturbances, and we know the disease can be transmitted unknowingly through corneal transplants,” explained Christina J. Sigurdson, DVM, Ph.D., professor of pathology at the University of California (UC) San Diego and UC Davis. “But the distribution and levels of prions in the eye were unknown. We have answered some of these questions. Our results have implications both for estimating the risk of CJD transmission and for the development of diagnostic tests for prion disease before symptoms become apparent.

The studies, conducted by scientists at UC San Diego and UC San Francisco in collaboration with a team from the National Institutes of Health (NIH), are reported in mBio, in an article entitled “Prion seeds spread in the eyes of sporadic patients with Creutzfeldt-Jakob disease. “

Prion diseases occur when misshapen prion proteins build up in the brain and cause damage that can lead to progressive neurodegeneration. CJD is the most common prion disease in humans and is classified as sporadic, familial, or iatrogenic (caused by treatment or medical procedure). While many people are aware of the very rare cases caused by eating beef infected with a similar disease, bovine spongiform encephalopathy or ‘mad cow disease’, around 85% of CJD cases are sporadic. having no known risk. The factors. About 10-15% of CJD cases in the United States are hereditary and linked to genetic mutations. In acquired CJD, prions are transmitted through medical procedures such as corneal transplants.

SCJD is often difficult to diagnose, the authors write, but visual disturbances are a common early symptom in about 10-20% of cases, and as the disease progresses, more than 40% of cases develop eye problems. Blindness will eventually develop in up to 42% of patients with CJD.

Previous studies have shown that the eyes of patients with CJD may contain infectious prions, but what is not yet understood is the distribution of prions to the different tissues of the eye. The risk of iatrogenic transmission of prions through ophthalmic procedures is not known, but there have likely been cases, the authors pointed out. “Corneal transplants from patients infected with prions have led to two probable and three possible cases of iatrogenic transmission of the prion. The risk of transmission from ophthalmic procedures is particularly significant given the increase in corneal transplant surgery worldwide. In the United States, for example, approximately 64,000 corneal transplants are performed each year.

The researchers used the highly sensitive and quantitative real-time tremor-induced conversion test (RT-QuIC) to look for prion seeding in eight different eye tissues, including the cornea, lens, eye fluid, retina and the optic nerve, in the post-eye mortem of 11 patients who died of sCJD. The RT-QuIC technique was developed by co-investigator Byron Caughey, Ph.D., at NIH Rocky Mountain Laboratories in Montana, and is used by clinicians to diagnose cCJD in people, typically via fluid. cerebrospinal and nasal brushing.

Used to analyze the eyes of patients with CJD, the test detected abnormal prions in several eye tissues, with the highest seed levels – which in some cases weren’t much lower than those in the brain – found in the retina. “We found that all 11 eyes of patients with cCJD were positive for prion seeding activity and had the highest seeding activity in the retina,” they wrote. “The levels of prion seeds in the retina were significantly higher than in extraocular muscles, optic nerve, cornea, lens, vitreous fluid, and sclera.”

The team claims that in addition to suggesting potential diagnostic utility, their findings also highlight ophthalmic surgery as a possible biohazard, and support recommendations for the use of disposable instruments or decontamination procedures to prevent transmission. iatrogenic prions. “Our results support the World Health Organization’s classification of ocular components as having high infectivity for prions and have implications for patient safety,” they noted. “Because the early phase of cCJD disease often includes visual symptoms, patients with cCJD will often have diagnostic evaluations performed by an ophthalmologist, which could contaminate the instruments. “

The researchers aim to continue their work by evaluating whether examining eye tissue and fluids using RT-QuIC could represent a diagnostic route for other neurodegenerative diseases characterized by abnormal protein accumulation. “Because other protein aggregates such as amyloid-β, -synuclein and tau protein can also spread from the brain to the retina, it would also be important to continue to assess the eyes of patients with neurodegenerative diseases. more common ones, such as Alzheimer’s disease, synucleinopathies, and tauopathies, especially in light of recent findings showing the prion-like spread of protein aggregates through the CNS.