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Title:   Author  item
                                            Greenlee, Justinitem
                                            Hamir, Amiraliitem
                                            WEST GREENLEE, M. HEATHER - IOWA STATE UNIVERSITY
  Submitted to: Veterinary Pathology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/25/2006
                                    Publication  Date: 9/1/2006
                                    Citation: Greenlee, J.J., Hamir, A.N., West Greenlee, M.H. 2006. Abnormal prion accumulation associated with retinal pathology in experimentally inoculated scrapie-affected sheep. Veterinary Pathology. 43:733-739.Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats affecting the nervous system.  After infection, the scrapie agent is known to accumulate in the brain, lymph nodes, and retina, the specialized sensory structure lining the inside of the eye.  All current methods of diagnosis for scrapie and related diseases require collection of brain tissue after death of the animal.  This study uses special staining techniques to show that accumulation of the agent causing scrapie in sheep is associated with pathology in the retina.  When small amounts of the agent causing scrapie were present in multiple, small areas of the retina, there was moderate positive staining to indicate cell injury.  In eyes (retinae) with large amounts of agent present, staining to indicate damage to retinal cells was very abundant and spread throughout the entire retina.  The inoculated animals were not examined for vision deficits, but the extent of special staining of damaged cells suggests that there may be functional deficits that could be measured possibly leading to new methods of disease diagnosis in live animals.  Results of this study will have a possible impact on directing future research on live animal diagnostic methods for transmissible spongiform encephalopathies.
                                Technical Abstract: The purpose of this study was to characterize the patterns of PrP**Sc immunoreactivity in the retinae of scrapie-infected sheep and determine the extent of retinal pathology as indicated by Glial Fibrillary Acidic Protein immunoreactivity (GFAP-IR) of Müller glia. GFAP-IR of Müller glia is suggestive of retinal pathology in absence of morphologic abnormality detected by light microscopy.  Sheep with the least amount of prion immunoreactivity have multifocal punctate aggregates of prion staining in the outer half of the inner plexiform layer and rarely in the outer plexiform layer.  In these retinae, GFAP-IR is not localized with prion accumulation, but rather is present in moderate numbers of Müller glia throughout the sections of retina examined.  The majority of affected retinae have intense, diffuse PrP**Sc staining in both plexiform layers with immunoreactivity in the cytoplasm of multifocal ganglion cells and lesser amounts in the optic fiber layer and between nuclei in nuclear layers. This intense PrP**Sc immunoreactivity is associated with diffuse, intense GFAP-IR from the inner limiting membrane to outer limiting membrane.  This is the first report of prion disease in a natural host to describe the accumulation of PrP**Sc in retina associated with retinal pathology without overt morphologic changes indicative of retinal degeneration.


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