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Prion Protein Accumulation in Eyes of Patients with Sporadic and Variant Creutzfeldt-Jakob Disease

¹From the National Creutzfeldt-Jakob Disease Surveillance Unit and Department of Pathology of the University of Edinburgh, Scotland, United Kingdom; and the ²Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.

PURPOSE. Creutzfeldt-Jakob disease (CJD) primarily affects the brain. This study was conducted to assess the possible involvement of the eye in sporadic and variant CJD by testing for the presence of the disease-associated, protease-resistant isoform of the prion protein (PrP^Sc) in ocular tissue.

METHODS. Human eyes from donors with CJD and non-prion neurodegenerative disease control eyes were studied. In situ hybridization and Western blot analysis were used to determine the normal pattern of cellular prion protein (PrP^C) expression. Western blot analysis and immunohistochemistry were then used to determine the localization, abundance, and isotype of PrP^Sc in eyes in CJD.

RESULTS. PrP^C was expressed in the nuclear layers of the retina. In both the sporadic and variant forms of CJD, PrP^Sc accumulated throughout the synaptic layers of the retina. The levels of PrP^Sc found in the retina were comparable with those found in the brain. Lower levels of PrP^Sc could be found in the optic nerve, but no PrP^Sc was detectable in other ocular tissues. The glycoform ratio of PrP^Sc in the retina did not correspond to that found in the brain.

CONCLUSIONS. Presumptive centrifugal spread of PrP^Sc from the brain through the optic nerve occurs in two major types of CJD. PrP^Sc is a marker of CJD infectivity. Given that routine decontamination may not remove PrP^Sc from surgical instruments, a careful risk assessment should be made of possible iatrogenic spread of sporadic and variant CJD after surgery to the retina or optic nerve.

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