Prion diseases are invariably fatal
neurodegenerative disorders that have gained much publicity due to their transmissible nature.
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common human
prion disorder, with an incidence of 1 in a million. Inherited
prion disorders are relatively rare, and associated with mutations in the
prion protein gene. More than 50 different point mutations, deletions, and insertions have been identified so far. Most are autosomal dominant and fully penetrant.
Prion disorders also occur in animals, and are of major concern because of the potential for spreading to humans. The principal pathogenic event underlying all
prion disorders is a change in the conformation of
prion protein (PrPC) from a mainly α-helical to a β-sheet rich
isoform, PrP-
scrapie (PrPSc). Accumulation of PrPSc in the brain parenchyma is the major cause of neuronal degeneration. The mechanism by which PrPSc is transmitted, propagates, and causes neurodegenerative changes has been investigated over the years, and several clues have emerged. Efforts are also ongoing for identifying specific and sensitive diagnostic tests for sCJD and animal
prion disorders, but success has been limited. The eye is suitable for these evaluations because it shares several anatomical and physiological features with the brain, and can be observed in vivo during
disease progression. The retina, considered an extension of the central nervous system, is involved extensively in
prion disorders. Accordingly, Optical Coherence Tomography and electroretinogram have shown some promise as pre-mortem diagnostic tests for human and animal
prion disorders. However, a complete understanding of the physiology of PrPC and pathobiology of PrPSc in the eye is essential for developing specific and sensitive tests. Below, we summarize recent progress in ocular physiology and pathology in
prion disorders, and the eye as an anatomically accessible site to diagnose, monitor
disease progression, and test therapeutic options.