Further ultrastructural studies of lesions produced in the optic nerve by tumor necrosis factor alpha (TNF-alpha): a comparison with experimental Creutzfeldt-Jakob disease.

We report here that intraocular injection of recombinant TNF-alpha produces lesions in the optic nerve indistinguishable from those reported for the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). The lesions were patchy and confined to the injected optic nerve. Axons show variable features of degenerations. Numerous vacuoles distended the myelin sheath. Hypertrophic astrocytes were numerous and many active macrophages containing digested myelin debris and lyre-like paracrystalline bodies. At high power, myelinated axons were observed as enveloped by astrocytic processes; formation of labyrinth-like network of such processes around damaged axons were observed. In conclusions, lesions produced by TNF-alpha mimic those of the panencephalopathic type of CJD, in direct support of our previous ultrastructural, immunohistochemical and molecular data on TNF-alpha involvement in CJD pathogenesis.