Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses
| Autor: | Bruce Chesebro, Brent Race, James F. Striebel, Cindi L. Schwartz, Jacqueline M. Leung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PrPSc Proteins genetic structures animal diseases Apoptosis Ribbon synapse Photoreceptor cell lcsh:RC346-429 chemistry.chemical_compound Mice 0302 clinical medicine Retinal Rod Photoreceptor Cells Parkinson Prion-like Microscopy Confocal Cell Death Chemistry Cell biology Retinitis pigmentosa medicine.anatomical_structure Disease Progression Retinal Cone Photoreceptor Cells Prion Retinal Bipolar Cells Ciliopathy Outer plexiform layer Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience Necrosis Ribbon synapses medicine Animals Retinal Photoreceptor Cell Inner Segment Outer nuclear layer Photoreceptor Connecting Cilium lcsh:Neurology. Diseases of the nervous system Retina Research Retinal medicine.disease Retinal Photoreceptor Cell Outer Segment nervous system diseases Microscopy Electron 030104 developmental biology Microscopy Fluorescence Alzheimer Neurology (clinical) sense organs 030217 neurology & neurosurgery Scrapie |
| Zdroj: | Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-26 (2021) Acta Neuropathologica Communications |
| ISSN: | 2051-5960 |
| Popis: | Accumulation of misfolded host proteins is central to neuropathogenesis of numerous human brain diseases including prion and prion-like diseases. Neurons of retina are also affected by these diseases. Previously, our group and others found that prion-induced retinal damage to photoreceptor cells in mice and humans resembled pathology of human retinitis pigmentosa caused by mutations in retinal proteins. Here, using confocal, epifluorescent and electron microscopy we followed deposition of disease-associated prion protein (PrPSc) and its association with damage to critical retinal structures following intracerebral prion inoculation. The earliest time and place of retinal PrPSc deposition was 67 days post-inoculation (dpi) on the inner segment (IS) of cone photoreceptors. At 104 and 118 dpi, PrPSc was associated with the base of cilia and swollen cone inner segments, suggesting ciliopathy as a pathogenic mechanism. By 118 dpi, PrPSc was deposited in both rods and cones which showed rootlet damage in the IS, and photoreceptor cell death was indicated by thinning of the outer nuclear layer. In the outer plexiform layer (OPL) in uninfected mice, normal host PrP (PrPC) was mainly associated with cone bipolar cell processes, but in infected mice, at 118 dpi, PrPSc was detected on cone and rod bipolar cell dendrites extending into ribbon synapses. Loss of ribbon synapses in cone pedicles and rod spherules in the OPL was observed to precede destruction of most rods and cones over the next 2–3 weeks. However, bipolar cells and horizontal cells were less damaged, indicating high selectivity among neurons for injury by prions. PrPSc deposition in cone and rod inner segments and on the bipolar cell processes participating in ribbon synapses appear to be critical early events leading to damage and death of photoreceptors after prion infection. These mechanisms may also occur in human retinitis pigmentosa and prion-like diseases, such as AD. |
| Databáze: | OpenAIRE |
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