title: Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy.
abstract: Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.
authors.affiliation: Department of Biomedical Sciences and Interdepartmental Toxicology Program, Iowa State University, Ames, IA 50010, United States of America.
authors.forename: M Heather West
authors.initials: MH
authors.lastname: Greenlee
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Ames, IA 50010, United States of America.
authors.forename: Jodi D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Genetics and Cell Biology and Interdepartmental Toxicology Program, Iowa State University, Ames, IA 50010, United States of America.
authors.forename: Ekundayo M
authors.initials: EM
authors.lastname: Platt
authors.affiliation: Department of Animal Science, Iowa State University, Ames, IA 50010, United States of America.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Juarez
authors.affiliation: Department of Animal Science, Iowa State University, Ames, IA 50010, United States of America.
authors.forename: Leo L
authors.initials: LL
authors.lastname: Timms
authors.affiliation: Virus and Prion Research Unit, National Animal Disease Center, Ames, IA 50010, United States of America.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Greenlee
mesh_terms: D000818:Animals; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence
chemical_list: D018620:PrPSc Proteins