Cell kinetics and cell death in the optic nerve of the myelin deficient rat.

The optic nerves of myelin deficient (md) and normal rats were studied by light microscopic thymidine autoradiography and electron microscopy during the first postnatal month. Mean total glial cell counts were similar at most ages in the md and normal optic nerves, but were significantly increased in the md nerves at 18 days of age, and significantly reduced at 30 days, compared to the controls. Labelling indices in the md optic nerves were significantly higher than control values at 16-25 days. Oligodendrocytes, astrocytes, microgliacytes and unclassified cells were labelled in both normal and md rats. The mutants showed higher percentages of labelled astroglia and microglia, and the labelled oligodendroglia appeared immature when compared to the normal animals. Md optic nerves showed significantly higher counts of necrotic cells than controls at 14-30 days. Electron microscopy revealed the presence of abnormal oligodendrocytes, characterized by distended rough endoplasmic reticulum and a dilated perinuclear envelope, from 6 days of age in the mutant. These cells appear to degenerate and die. These results suggest a defect in the md rat oligodendrocyte, resulting in a protracted uptake of thymidine and increased cell death. Investigation of the link between these observations and the proposed myelin proteolipid protein defect in the md rat may reveal more about the role of myelin proteins in the CNS, and the specific cellular defect(s) in this mutant.