Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses

摘要: Accumulation of misfolded host proteins is central to neuropathogenesis numerous human brain diseases including prion and prion-like diseases. Neurons retina are also affected by these Previously, our group others found that prion-induced retinal damage photoreceptor cells in mice humans resembled pathology retinitis pigmentosa caused mutations proteins. Here, using confocal, epifluorescent electron microscopy we followed deposition disease-associated protein (PrPSc) its association with critical structures following intracerebral inoculation. The earliest time place PrPSc was 67 days post-inoculation (dpi) on the inner segment (IS) cone photoreceptors. At 104 118 dpi, associated base cilia swollen segments, suggesting ciliopathy as a pathogenic mechanism. By deposited both rods cones which showed rootlet IS, cell death indicated thinning outer nuclear layer. In plexiform layer (OPL) uninfected mice, normal PrP (PrPC) mainly bipolar processes, but infected at detected rod dendrites extending into ribbon synapses. Loss synapses pedicles spherules OPL observed precede destruction most over next 2–3 weeks. However, horizontal were less damaged, indicating high selectivity among neurons for injury prions. segments processes participating appear be early events leading photoreceptors after infection. These mechanisms may occur diseases, such AD.