title: The toxicity of the PrP106-126 prion peptide on cultured photoreceptors correlates with the prion protein distribution in the mammalian and human retina.
abstract: 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 into the retinal pathophysiology of prion diseases and illustrate advantages of adult retinal cell cultures to investigate prion pathogenic mechanisms.
authors: INSERM U592, Bâtiment Kourilsky, 184 rue du Faubourg Saint-Antoine, F-75571 Paris Cedex 12, France.
authors: Jie
authors: J
authors: Gong
authors: Abdeljelil
authors: A
authors: Jellali
authors: Valérie
authors: V
authors: Forster
authors: Jérôme
authors: J
authors: Mutterer
authors: Elisabeth
authors: E
authors: Dubus
authors: Wilko D
authors: WD
authors: Altrock
authors: José A
authors: JA
authors: Sahel
authors: Alvaro
authors: A
authors: Rendon
authors: Serge
authors: S
authors: Picaud
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D010786:Photoreceptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D013552:Swine; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions