Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, incurable neurological disease characterized by a progressive decline in motor control and cognitive ability that leads, ultimately, to a comatose state and death. Caused by infectious misfolded proteins, sCJD is one of several poorly understood fatal brain disorders within the category of transmissible spongiform encephalopathies (TSEs) – aka prion diseases.
Because sCJD presents with diverse symptoms, wide-ranging rate of decline, and may target a variety of brain areas, physicians often struggle to diagnose the illness. This challenge makes the already devastating disease course even more frustrating for patients and their families and creates situations that are dangerous to others, as sCJD can be spread through contact with improperly sterilized medical instruments or through transplanted organs and tissue donated by deceased patients whose disease was not identified. In fact, medical investigators have found two confirmed and three suspected cases where an individual died from sCJD after receiving an infected corneal transplant.
But to make the already hazy picture of CJD more confusing, past investigations have found conflicting results on whether infectious prions are harbored in the eye. Hoping to add clarity, scientists from the University of California system and the National Institutes of Health (NIH) joined forces to conduct the most comprehensive analysis of sCJD in ocular tissue.
Their study, published in mBio, found the abnormal proteins in all 11 sCJD eyes analyzed.
"Almost half of sCJD patients develop visual disturbances, and we know that the disease can be unknowingly transmitted through corneal graft transplantation," author Dr Christina Sigurdson said in a statement. "But distribution and levels of prions in the eye were unknown. We've answered some of these questions. Our findings have implications for both estimating the risk of sCJD transmission and for development of diagnostic tests for prion diseases before symptoms become apparent."
The work was made possible by a new testing platform – the real-time quaking-induced conversion (RT-QuIC) assay, developed by co-author Byron Caughey – that can quickly and accurately detect sCJD prions in tissue and fluids.
“The retina consistently showed the highest seed levels, which in some cases were only slightly lower than brain,” the team wrote. “Prion seeds were also present in the optic nerve, extraocular muscle, choroid, lens, vitreous, and sclera.”
Crucially, all 11 eyes – willed to the researchers by CJD patients before their death – showed prions in the cornea, which is the layer of transparent tissue that covers the iris and pupil. The implications of this finding are simultaneously unsettling and exciting.
“Collectively, these results reveal that sCJD patients accumulate prion seeds throughout the eye, indicating the potential diagnostic utility as well as a possible biohazard,” the authors continued.
Corneal transplants are one of the most common types of transplant worldwide. As of now, the donated tissue is not routinely tested for prions before implantation.
Moving forward, the team plan to further assess the RT-QuIC's efficacy in detecting prions in eye tissue. Currently, it is used on cerebrospinal fluid and nasal tissue. In the future, they believe the technology could be applied to test for the presence of the protein aggregates associated with Parkinson's disease and Lewy body dementia.
In regards to the now-apparent biohazard risk of CJD patients' eyes, the team recommends that ophthalmologists should switch to single-use instruments or more intensive equipment decontamination procedures and call for increased research into new synthetic corneal implant options.