Degree Type

Dissertation

Date of Award

2008

Degree Name

Doctor of Philosophy

Department

Biomedical Sciences

First Advisor

M. Heather West Greenlee

Second Advisor

M. Heather West Greenlee

Third Advisor

Justin Greenlee

Abstract

Transmissible spongiform encephalopathies (TSE) encompass a group of unique, invariably fatal neurodegenerative diseases, which affect humans and animals. Accumulation of an abnormal form of the prion protein (PrPSc) in the central nervous system serves as their pathologic underpinning. The pathogenesis of TSE remains unclear, and the specific effects of PrPSc on cells of the nervous system have yet to be completely resolved. Previous studies have identified the accumulation of PrP Sc within the retina, the thin, highly organized piece of neural tissue lining the posterior aspect of the eye. The purpose of this dissertation was to investigate the effects of PrPSc accumulation on retinal cellular morphology and function.;Using morphologic and functional analyses, we have identified alterations in retinal cellular morphology and function in sheep and cattle infected with TSE. We examined the effects of PrPSc on retinal cellular morphology in sheep affected with their naturally occurring TSE, scrapie, using immunohistochemistry (IHC). We demonstrated alteration of immunoreactivity patterns of rod bipolar cell, retinal ganglion cell, and Muller glia specific markers. Immunoreactivity patterns of cholinergic amacrine cell and conventional synapse markers were similar to scrapie free control sheep. In cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy (TME), we combined functional (electroretinography) and morphologic (IHC) analyses to investigate the impact of TSE infection on the bovine retina. We demonstrated altered retinal function during the preclinical phase of disease, evidenced by prolonged ERG b-wave implicit time, and during the clinical phase, evidenced by prolonged implicit time and decreased amplitude of the b-wave. Morphologic abnormalities consistent with spongiform change were demonstrated in the retina of TME-affected cattle, and immunoreactivity patterns of rod bipolar cell and Muller glia markers were altered. Our results contribute novel and important information on the response of the retina to TSE.

DOI

https://doi.org/10.31274/rtd-180813-16987

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Jodi D. Smith

Language

en

Proquest ID

AAI3383370

OCLC Number

492198355

ISBN

9781109454789

File Format

application/pdf

File Size

62 pages

Share

COinS