Purpose: Both in vitro and in vivo studies have implicated a role for tumor necrosis factor (TNF-alpha) in the pathology of demyelinating diseases. The purpose of this study was to address the hypothesis that TNF-alpha is a mediator of AIDS-related optic nerve injury and to determine the cell types involved in the proliferation of TNF-alpha in the AIDS optic nerve.
Methods: Ten optic nerves from seven patients with AIDS, and three from persons who were HIV negative were stained, using the indirect immunoperoxidase method. Six of the ten AIDS optic nerves were positive for cytomegalovirus (CMV), but the remainder did not have abnormal fundus findings.
Results: In all the optic nerves from AIDS patients with or without CMV retinitis, the vast majority of astrocytes stained strongly for TNF-alpha. Microglial cells (MPS-derived macrophages) varied from not staining to staining strongly positive for TNF-alpha. However, oligodendrocytes were not labeled positively for TNF-alpha. Some endothelial cells also stained for TNF-alpha. Examination of normal optic nerves and controls did not reveal any cell type that stained positively for TNF-alpha.
Conclusions: The present study supports the contention that TNF-alpha is a major mediator of AIDS-associated optic neuropathy. HIV infection induces the production of TNF-alpha in macrophages and astrocytes, which probably causes demyelination and other neuronal damage.