Creutzfeldt-Jakob disease

Sèze, Jérôme De; Hache, J.-C.; Vermersch, Patrick; Arndt, Carl; Maurage, Claude‐Alain; Pasquier, Florence; Laplanche, Jean‐Louis; Mm, Ruchoux; Leys, D.; Destée, Alain; Petit, H

doi:10.1212/wnl.51.4.962

Cited by 31 publications

(28 citation statements)

References 13 publications

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“…32 It could further explain the disappearance or spongiform aspect of the outer plexiform layer in patients with Creutzfeldt-Jakob disease. 5 PrP c was also located in amacrine cell terminals, consistent with previous observations of the native and protease-resistant protein in the IPL. 7,32,33 This location could also explain the histological damage occasionally observed in the IPL of patients affected by Creutzfeldt-Jakob disease.…”

Section: Prp C Localization In the Retinasupporting

confidence: 91%

“…6 In histology, major spongiform changes were observed in the outer plexiform layer (OPL) where photoreceptors have their synaptic terminals, and only moderate changes were observed in the inner plexiform layer (IPL) and ganglion cell layer. 5 These localizations were consistent with the reported accumulation of the pathogenic form of the prion protein, PrP res , throughout the plexiform layers of the human retina. 7 The in vivo retina has been used on many occasions to study the progression of the disease in animal models because of its organized structure, its in vivo access for intraocular injection, and the possibility to correlate the histology to the measure of neuronal function by the electroretinogram.…”

supporting

confidence: 87%

“…1 These neurological disorders exhibit common pathological symptoms like vacuolization of the neurophils, astrocytosis, and loss of neurons. 2 In patients with CreutzfeldtJakob disease, alteration of the retinal function was attested by the decrease in the electroretinogram b-wave amplitude, [3][4][5] which reflects the activity of bipolar cells postsynaptic to photoreceptors. These early electroretinogram changes were even proposed as a diagnostic measurement for the disease.…”

mentioning

confidence: 99%

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The Toxicity of the PrP106-126 Prion Peptide on Cultured Photoreceptors Correlates with the Prion Protein Distribution in the Mammalian and Human Retina

Gong

Jellali

Forster

et al. 2007

The American Journal of Pathology

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In patients affected by Creutzfeldt-Jakob disease and in animals affected by transmissible spongiform encephalopathies, retinal functions are altered, and major spongiform changes are observed in the outer plexiform layer where photoreceptors have their synaptic terminals. In the present study, the prion protein PrP c was found to form aggregates in rod photoreceptor terminals from both rat and human retina, whereas no labeling was observed in cone photoreceptors. Discrete staining was also detected in the inner plexiform layer where the prion protein was located at human amacrine cell synapses. In mixed porcine retinal cell cultures, the PrP106-126 prion peptide triggered a 61% rod photoreceptor cell loss by apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling, whereas cone photoreceptors were not affected. Amacrine cells were also reduced by 47% in contrast to ganglion cells. Although this cell loss was associated with a 5.5-fold increase in microglial cells, the strict correlation between the PrP c prion protein expression and the peptide toxicity suggested that this toxicity did not rely on the release of a toxic compound by glial cells. These results provide new insights Transmissible spongiform encephalopathies in humans and in animals are linked to the transconformation of the prion protein PrP c into a proteinase-resistant form PrP res . 1 These neurological disorders exhibit common pathological symptoms like vacuolization of the neurophils, astrocytosis, and loss of neurons. 2 In patients with CreutzfeldtJakob disease, alteration of the retinal function was attested by the decrease in the electroretinogram b-wave amplitude, 3-5 which reflects the activity of bipolar cells postsynaptic to photoreceptors. These early electroretinogram changes were even proposed as a diagnostic measurement for the disease. 6 In histology, major spongiform changes were observed in the outer plexiform layer (OPL) where photoreceptors have their synaptic terminals, and only moderate changes were observed in the inner plexiform layer (IPL) and ganglion cell layer. 5 These localizations were consistent with the reported accumulation of the pathogenic form of the prion protein, PrP res , throughout the plexiform layers of the human retina. 7 The in vivo retina has been used on many occasions to study the progression of the disease in animal models because of its organized structure, its in vivo access for intraocular injection, and the possibility to correlate the

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Section: Prp C Localization In the Retinasupporting

confidence: 91%

supporting

confidence: 87%

mentioning

confidence: 99%

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The Toxicity of the PrP106-126 Prion Peptide on Cultured Photoreceptors Correlates with the Prion Protein Distribution in the Mammalian and Human Retina

Gong

Jellali

Forster

et al. 2007

The American Journal of Pathology

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“…1 Similar to ERG reports from Creutzfeldt-Jakob disease-affected patients, 7,18 bwave amplitude was decreased in 2 clinically affected TME cattle. This observed decrease in b- Sc accumulation in the retina and its associated pathology.…”

Section: Discussionsupporting

confidence: 62%

Retinal Function and Morphology Are Altered in Cattle Infected with the Prion Disease Transmissible Mink Encephalopathy

et al. 2009

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Abstract. Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein-contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy (''mad cow disease'') to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy-inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy-infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Mü ller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of new strategies for the diagnosis of TSEs.

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“…These results suggest that the nonfibrillar P118 -135 peptide causes retinal cell death but weakly damages the photoreceptor cells. Interestingly, patients with Creutzfeldt-Jakob disease have been reported to present a selective loss of the b-wave amplitude without alteration of the a-wave amplitude (de Seze et al, 1998;Katz et al, 2000). Further experiments will be performed to precisely define the retinal cell type affected by P118 -135 toxic effects.…”

Section: Discussionmentioning

confidence: 99%

In VivoandIn VitroNeurotoxicity of the Human Prion Protein (PrP) Fragment P118–135 Independently of PrP Expression

Chabry

Ratsimanohatra²,

Sponne

et al. 2003

J. Neurosci.

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We recently demonstrated that the 118 -135 putative transmembrane domain of prion protein (PrP) exhibited membrane fusogenic properties and induced apoptotic neuronal cell death of rat cortical neurons, independently of its aggregation state. The aim of the present study was to analyze the in vivo neurotoxicity of the prion fragment P118 -135 and to evaluate the potential role of the physiological isoform of PrP in the P118 -135-induced cell death. Here, we demonstrate that the nonfibrillar P118 -135 is cytotoxic to retinal neurons in vivo as monitored by intravitreal inoculation and recording of the electrical activity of retina and tissue examination. Moreover, knock-out PrP gene mice exhibit similar sensitivity to the nonfibrillar P118 -135-induced cell death and electrical perturbations, strongly suggesting that cell death occurs independently of PrP expression. Interestingly, a variant nonfusogenic P118 -135 peptide (termed P118 -135) had no effects on in vivo neuronal viability, suggesting that the P118 -135-induced cell death is mediated by its membrane destabilizing properties. These data have further been confirmed in vitro. We show that the fusogenic peptide P118 -135 induces death of cultured neurons from both wild-type and knock-out PrP gene mice via an apoptotic-mediated pathway, involving early caspase activation and DNA fragmentation. Altogether these results emphasize the neurotoxicity of the fusogenic nonfibrillar PrP transmembrane domain and indicate that fibril formation and PrP expression are not obligatory requirements for neuronal cell death. The use of synthetic prion peptides could provide insights into the understanding of neuronal loss mechanisms that take place during the development of the various types of spongiform encephalopathies.

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Creutzfeldt-Jakob disease

Abstract: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.

Cited by 31 publications

References 13 publications

The Toxicity of the PrP106-126 Prion Peptide on Cultured Photoreceptors Correlates with the Prion Protein Distribution in the Mammalian and Human Retina

The Toxicity of the PrP106-126 Prion Peptide on Cultured Photoreceptors Correlates with the Prion Protein Distribution in the Mammalian and Human Retina

Retinal Function and Morphology Are Altered in Cattle Infected with the Prion Disease Transmissible Mink Encephalopathy

In VivoandIn VitroNeurotoxicity of the Human Prion Protein (PrP) Fragment P118–135 Independently of PrP Expression

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