Pathological findings in retina and visual pathways associated to natural Scrapie in sheep

Hortells, Paloma; Monzón, Marta; Monleón, Eva; Acín, Cristina; Vargas, Antonia; Bolea, Rosa; Luján, Lluís; Badiola, Juan José

doi:10.1016/j.brainres.2006.06.021

Cited by 31 publications

(56 citation statements)

References 19 publications

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“…These histopathological lesions were associated with PrP Sc deposition in all of the cases and alterations in the retinal glia manifested as an increased expression of the intermediate filament GFAP. In a recent report, only 50% of sheep with signs of natural scrapie were found to have retinal degenerative lesions [16]. In our affected sheep, the multifocal accumulation of amorphous material within the subretinal space was less marked than in the two cases reported by Barnett and Palmer [15].…”

Section: Discussioncontrasting

confidence: 58%

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Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie

et al. 2011

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BackgroundThe retina is part of the diencephalon in a peripheral location and may be involved in prion diseases. Retinal function and structural changes were assessed in naturally scrapie-affected red face Manech ewes presenting the classical signs of the disease, and clinically healthy age-matched subjects for controls. Ophthalmic examination was done prior to electroretinography (ERG), which was carried out under conditions that allowed photopic and scotopic activities to be assessed. Histomorphometry of the inner and outer retinal layers was performed post-mortem, and retinas were also examined for evidence of abnormal prion protein (PrPSc) accumulation and glial fibrillary acidic protein (GFAP) upregulation as a marker of gliosis. Scrapie status was determined by examination of brain tissueResultsOcular reflexes and ophthalmoscopy did not reveal any difference between scrapie affected and control animals. Although the light-and dark-adapted ERG responses of both rod-and cone-mediated functions had a similar waveform in scrapie-affected and control sheep, a significant reduction in the amplitude of the ERG a-and b-waves was observed in affected animals compared to controls. These functional alterations were correlated with a substantial loss of cells in the outer nuclear layer (ONL), lengthening and disorganization in photoreceptor segments, and substantial reduction in cellularity and thickness of the inner nuclear layer (INL). The degenerative changes in the INL and ONL were most marked in the central and paracentral areas of the scrapie retinas, and were accompanied in all scrapie retinas by PrPSc deposition in the ganglion cell and synaptic layers. GFAP immunoreactivity was mainly increased in the ganglion cell and inner plexiform layers.ConclusionsNo appreciable fundoscopic changes were observed in the scrapie-affected ewes although reproducible changes in retinal function as measured by ERG were observed in these animals. The alterations in the receptoral and post-receptoral pathways corresponded to the degenerative lesions observed in the ONL and INL of the scrapie retinas. The retinal degeneration was associated with prion protein infectivity which presumably spread via the optic nerve.

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Section: Discussioncontrasting

confidence: 58%

“…Previous studies assessing the retinal changes in sheep with natural scrapie have been performed, but without morphometric analysis [15,16], and information on the activity of the retina in scrapie-infected sheep is presently limited to one case report [17]. …”

Section: Introductionmentioning

confidence: 99%

Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie

et al. 2011

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“…We and others have demonstrated that PrP Sc accumulates in the retinas of animals infected with TSEs [1,17–27]. The retina is the most accessible part of the CNS and is amenable to non-invasive assessment of morphology and function.…”

Section: Introductionmentioning

confidence: 99%

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

et al. 2015

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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.

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“…inoculation with the mouse scrapie strain ME7 (17,37,47,48). Furthermore, recent work using scrapie infection of sheep has validated the importance of this model in a natural infection and indicated the retina and brain visual system as a prominent site of PrP-res accumulation and pathology (21).…”

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confidence: 96%

Prion Protein Expression Differences in Microglia and Astroglia Influence Scrapie-Induced Neurodegeneration in the Retina and Brain of Transgenic Mice

Kercher

Favara

Striebel

et al. 2007

J Virol

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Activated microglia and astroglia are known to be involved in a variety of neurodegenerative diseases, including prion diseases. In the present experiments, we studied activation of astroglia and microglia after intraocular scrapie infection in transgenic mice expressing prion protein (PrP) in multiple cell types (tg7 mice) or in neurons only (tgNSE mice). In this model, scrapie infection and protease-resistant PrP deposition occurs in the retinas of both strains of mice, but retinal degeneration is observed only in tg7 mice. Our results showed that the retinas of tg7 and tgNSE mice both had astroglial activation with increased chemokine expression during the course of infection. However, only tg7 retinas exhibited strong microglial activation compared to tgNSE retinas, which showed little microglial activation by biochemical or morphological criteria. Therefore, microglial PrP expression might be required for scrapie-induced retinal microglial activation and damage. Furthermore, microglial activation preceded retinal neurodegeneration in tg7 mice, suggesting that activated microglia might contribute to the degenerative process, rather than being a response to the damage. Surprisingly, brain differed from retina in that an altered profile of microglial activation markers was upregulated, and the profiles in the two mouse strains were indistinguishable. Microglial activation in the brain was associated with severe brain vacuolation and neurodegeneration, leading to death. Thus, retinal and brain microglia appeared to differ in their requirements for activation, suggesting that different activation pathways occur in the two tissues.

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Pathological findings in retina and visual pathways associated to natural Scrapie in sheep

Cited by 31 publications

References 19 publications

Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie

Clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

Prion Protein Expression Differences in Microglia and Astroglia Influence Scrapie-Induced Neurodegeneration in the Retina and Brain of Transgenic Mice

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