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Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common prion disease in humans and has been iatrogenically transmitted through corneal graft transplantation. Approximately 40% of sCJD patients develop visual or oculomotor symptoms and may seek ophthalmological consultation. Here we used the hi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247090/ https://www.ncbi.nlm.nih.gov/pubmed/30459197 http://dx.doi.org/10.1128/mBio.02095-18 |
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author | Orrù, Christina D. Soldau, Katrin Cordano, Christian Llibre-Guerra, Jorge Green, Ari J. Sanchez, Henry Groveman, Bradley R. Edland, Steven D. Safar, Jiri G. Lin, Jonathan H. Caughey, Byron Geschwind, Michael D. Sigurdson, Christina J. |
author_facet | Orrù, Christina D. Soldau, Katrin Cordano, Christian Llibre-Guerra, Jorge Green, Ari J. Sanchez, Henry Groveman, Bradley R. Edland, Steven D. Safar, Jiri G. Lin, Jonathan H. Caughey, Byron Geschwind, Michael D. Sigurdson, Christina J. |
author_sort | Orrù, Christina D. |
collection | PubMed |
description | Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common prion disease in humans and has been iatrogenically transmitted through corneal graft transplantation. Approximately 40% of sCJD patients develop visual or oculomotor symptoms and may seek ophthalmological consultation. Here we used the highly sensitive real-time quaking-induced conversion (RT-QuIC) assay to measure postmortem prion seeding activities in cornea, lens, ocular fluid, retina, choroid, sclera, optic nerve, and extraocular muscle in the largest series of sCJD patient eyes studied by any assay to date. We detected prion seeding activity in 100% of sCJD eyes, representing three common sCJD subtypes, with levels varying by up to 4 log-fold among individuals. The retina consistently showed the highest seed levels, which in some cases were only slightly lower than brain. Within the retina, prion deposits were detected by immunohistochemistry (IHC) in the retinal outer plexiform layer in most sCJD cases, and in some eyes the inner plexiform layer, consistent with synaptic prion deposition. Prions were not detected by IHC in any other eye region. With RT-QuIC, prion seed levels generally declined in eye tissues with increased distance from the brain, and yet all corneas had prion seeds detectable. Prion seeds were also present in the optic nerve, extraocular muscle, choroid, lens, vitreous, and sclera. Collectively, these results reveal that sCJD patients accumulate prion seeds throughout the eye, indicating the potential diagnostic utility as well as a possible biohazard. |
format | Online Article Text |
id | pubmed-6247090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62470902018-11-30 Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients Orrù, Christina D. Soldau, Katrin Cordano, Christian Llibre-Guerra, Jorge Green, Ari J. Sanchez, Henry Groveman, Bradley R. Edland, Steven D. Safar, Jiri G. Lin, Jonathan H. Caughey, Byron Geschwind, Michael D. Sigurdson, Christina J. mBio Research Article Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common prion disease in humans and has been iatrogenically transmitted through corneal graft transplantation. Approximately 40% of sCJD patients develop visual or oculomotor symptoms and may seek ophthalmological consultation. Here we used the highly sensitive real-time quaking-induced conversion (RT-QuIC) assay to measure postmortem prion seeding activities in cornea, lens, ocular fluid, retina, choroid, sclera, optic nerve, and extraocular muscle in the largest series of sCJD patient eyes studied by any assay to date. We detected prion seeding activity in 100% of sCJD eyes, representing three common sCJD subtypes, with levels varying by up to 4 log-fold among individuals. The retina consistently showed the highest seed levels, which in some cases were only slightly lower than brain. Within the retina, prion deposits were detected by immunohistochemistry (IHC) in the retinal outer plexiform layer in most sCJD cases, and in some eyes the inner plexiform layer, consistent with synaptic prion deposition. Prions were not detected by IHC in any other eye region. With RT-QuIC, prion seed levels generally declined in eye tissues with increased distance from the brain, and yet all corneas had prion seeds detectable. Prion seeds were also present in the optic nerve, extraocular muscle, choroid, lens, vitreous, and sclera. Collectively, these results reveal that sCJD patients accumulate prion seeds throughout the eye, indicating the potential diagnostic utility as well as a possible biohazard. American Society for Microbiology 2018-11-20 /pmc/articles/PMC6247090/ /pubmed/30459197 http://dx.doi.org/10.1128/mBio.02095-18 Text en https://doi.org/10.1128/AuthorWarrantyLicense.v1 This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. |
spellingShingle | Research Article Orrù, Christina D. Soldau, Katrin Cordano, Christian Llibre-Guerra, Jorge Green, Ari J. Sanchez, Henry Groveman, Bradley R. Edland, Steven D. Safar, Jiri G. Lin, Jonathan H. Caughey, Byron Geschwind, Michael D. Sigurdson, Christina J. Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title | Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title_full | Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title_fullStr | Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title_full_unstemmed | Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title_short | Prion Seeds Distribute throughout the Eyes of Sporadic Creutzfeldt-Jakob Disease Patients |
title_sort | prion seeds distribute throughout the eyes of sporadic creutzfeldt-jakob disease patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247090/ https://www.ncbi.nlm.nih.gov/pubmed/30459197 http://dx.doi.org/10.1128/mBio.02095-18 |
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