Morphological changes in oligodendrocytes in the intact mouse optic nerve following intravitreal injection of tumour necrosis factor

Abstract

Intracellular dye-injection was used to determine the whole-cell morphology of oligodendrocytes in intact optic nerves of mice following intravitreal injection of tumour necrosis factor-α (TNFα) or heat-inactivated TNFα to act as controls. Oligodendrocytes in control nerves had a stereotypic morphology, and provided an average of 20 axons with single internodal myelin segments of around 200 μm internodal length. Oligodendrocytes with abnormal morphological features were identified 8–18 days following intravitreal injection of TNFα. Internodal myelin segments developed swellings along their lengths, became attenuated, and in extreme cases receded completely. This study provides a new insight into the process of demyelination, especially of the early stages which are not amenable with other techniques. Furthermore, it confirms that injection of TNFα into the vitreous, a fluid compartment of the CNS, instigates a sequence of events which results in oligodendrocyte disruption and demyelination. The mechanism by which intravitreally injected TNFα mediates these changes in optic nerve oligodendrocytes are yet unknown.