Campus Units

Biomedical Sciences

Document Type

Article

Publication Version

Published Version

Publication Date

9-2016

Journal or Book Title

The American Journal of Pathology

Volume

186

Issue

9

First Page

2302

Last Page

2309

DOI

10.1016/j.ajpath.2016.05.018

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 (PrPSc) from the brain to the retina, the accumulation of PrPSc 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 PrPSc and the resulting response of retinal tissue. Loss of photoreceptors was used as a measure of neuronal death. PrPSc seeding activity was first detected in all samples at 60 dpi. Accumulation of PrPSc 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.

Comments

This article is published as Greenlee, M. Heather West, Melissa Lind, Robyn Kokemuller, Najiba Mammadova, Naveen Kondru, Sireesha Manne, Jodi Smith, Anumantha Kanthasamy, and Justin Greenlee. "Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie." The American journal of pathology 186, no. 9 (2016): 2302-2309. doi: 10.1016/j.ajpath.2016.05.018.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf