MORPHOLOGICAL-CHANGES IN OLIGODENDROCYTES IN THE INTACT MOUSE OPTIC-NERVE FOLLOWING INTRAVITREAL INJECTION OF TUMOR-NECROSIS-FACTOR

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-alpha (TNF alpha) or heat-inactivated TNF alpha 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 mu m internodal length. Oligodendrocytes with abnormal morphological features were identified 8-14 days following intravitreal injection of TNF alpha. 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 TNF alpha 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 TNF alpha mediates these changes in optic nerve oligodendrocytes are yet unknown.