Ultrastructural alterations in the optic nerve in transmissible spongiform encephalopathies or prion diseases--a review.

The involvement of the visual system is well recognised in TSEs. The present review summarises the ultrastructural changes in the optic nerves in experimental infections of laboratory rodents with the agents of two human TSEs (CJD and GSS) and with two isolates of the scrapie agent. Vacuoles of myelinated fibres were found within myelin sheaths and themselves contained secondary vacuoles (vacuoles within other vacuoles) and curled membrane fragments not unlike the vacuoles in cerebral grey matter (see also: Spongiform change--an electron microscopic view; this issue). The myelin sheath had split either at the major dense line or at the intraperiod line. In addition, axons contained vacuoles within the axoplasm, corresponding to the typical spongiform vacuoles of grey matter. Vacuolation of myelinated fibres was accompanied by an exuberant cellular reaction consisting of macrophages containing numerous mitochondria, abundant rough endoplasmic reticulum and secondary lysosomes filled with digested myelin debris, electron-dense material and sometimes entire myelin-bounded vacuoles. Within macrophages myelin fragments undergoing active digestion were often seen, together with lyre-like bodies and paracrystalline inclusions. Astrocytes and their processes were prominent and glial filaments and many mitochondria were readily detected. Proliferation of the inner mesaxons was also seen. Cross-sectional profiles of many myelinated fibres contained membranous organelles continuous with the inner lamellae of the oligodendroglial cells. The inner mesaxon proliferations formed whorls and loops. In some axons proliferation was so severe that the mesaxonal loops filled the whole cross-section of the axon. Occasionally there was intrusion of the membranous tongue of the inner mesaxon into the axoplasm. Dystrophic neurites were relatively numerous. In GSS-infected animals some axons underwent demyelination with stripping of the myelin lamellae, while still others underwent vesicular myelin degeneration. It is of special note that in the cytoplasm of several cells as well as the axoplasm numerous autophagic vacuoles were seen.