Prion diseases are a group of neurodegenerative disorders that are caused by the deposition of abnormally folded proteins in the brain. Prion diseases primarily involve the brain, but also can affect the eyes and other organs. A new study by scientists at the National Institutes of Health reports that the earliest eye damage from prion disease takes place in the cone photoreceptor cells, specifically in the cilia and the ribbon synapses. Their findings may offer insights on human retinitis pigmentosa, an inherited disease with similar photoreceptor degeneration leading to blindness.

Their findings, “Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses,” are published in the journal Acta Neuropathologica Communications.

In their study, the scientists, from NIH’s National Institute of Allergy and Infectious Diseases at Rocky Mountain Laboratories in Hamilton, Montana, used laboratory mice infected with scrapie, a prion disease common to sheep and goats. Scrapie is closely related to human prion diseases, such as variant, familial, and sporadic Creutzfeldt-Jakob disease (CJD).

“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,” the researchers wrote. “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.”

Their work suggests that by interfering with transport through cilia, these aggregates may provide an important early mechanism by which prion infection selectively destroys photoreceptors. Prion protein also was deposited in cones and rods adjacent to ribbon synapses just before the destruction of these structures and death of photoreceptors. Ribbon synapses are specialized neuron connections found in ocular and auditory neural pathways, and their health is critical to the function of retinal photoreceptors in the eye, as well as hair cells in the ear.

The identification of disease-associated prion protein, and the correlation with retinal damage, has not been seen previously and is likely to occur in all prion-susceptible species, including people.

Looking toward the future, the researchers are hoping to study whether similar findings occur in the retinas of people with other degenerative diseases characterized by misfolded-host proteins, such as Alzheimer’s and Parkinson’s diseases.

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