title: Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie.
abstract: Currently, there is a lack of pathological landmarks to describe the progression of prion disease in vivo. Our goal was to use an experimental model to determine the temporal relationship between the transport of misfolded prion protein (PrP(Sc)) from the brain to the retina, the accumulation of PrP(Sc) in the retina, the response of the surrounding retinal tissue, and loss of neurons. Retinal samples from mice inoculated with RML scrapie were collected at 30, 60, 90, 105, and 120 days post inoculation (dpi) or at the onset of clinical signs of disease (153 dpi). Retinal homogenates were tested for prion seeding activity. Antibody staining was used to assess accumulation of PrP(Sc) and the resulting response of retinal tissue. Loss of photoreceptors was used as a measure of neuronal death. PrP(Sc) seeding activity was first detected in all samples at 60 dpi. Accumulation of PrP(Sc) and coincident activation of retinal glia were first detected at 90 dpi. Activation of microglia was first detected at 105 dpi, but neuronal death was not detectable until 120 dpi. Our results demonstrate that by using the retina we can resolve the temporal separation between several key events in the pathogenesis of prion disease.
authors: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa; Virus and Prion Disease Unit, National Animal Disease Center, US Department of Agriculture, Ames, Iowa. Electronic address: mheather@iastate.edu.
authors: M Heather
authors: MH
authors: West Greenlee
authors: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa.
authors: Melissa
authors: M
authors: Lind
authors: Virus and Prion Disease Unit, National Animal Disease Center, US Department of Agriculture, Ames, Iowa.
authors: Robyn
authors: R
authors: Kokemuller
authors: Virus and Prion Disease Unit, National Animal Disease Center, US Department of Agriculture, Ames, Iowa.
authors: Najiba
authors: N
authors: Mammadova
authors: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa.
authors: Naveen
authors: N
authors: Kondru
authors: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa.
authors: Sireesha
authors: S
authors: Manne
authors: Virus and Prion Disease Unit, National Animal Disease Center, US Department of Agriculture, Ames, Iowa.
authors: Jodi
authors: J
authors: Smith
authors: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa.
authors: Anumantha
authors: A
authors: Kanthasamy
authors: Virus and Prion Disease Unit, National Animal Disease Center, US Department of Agriculture, Ames, Iowa.
authors: Justin
authors: J
authors: Greenlee
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D012160:Retina / Q000473:pathology*
chemical_list: D018620:PrPSc Proteins