AN IMMUNOHISTOCHEMICAL STUDY OF TNF-ALPHA IN OPTIC NERVES FROM AIDS PATIENTS

Purpose. Both in vitro and in vivo studies have implicated a role for tumor necrosis factor (TNF-alpha) in the pathology of demyelinating di seases. The purpose of this study was to address the hypothesis that T NF-alpha is a mediator of AIDS-related optic nerve injury rind to dete rmine 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, usin g the indirect immunoperoxidase method. Six of the ten AIDS optic nerv es were positive for cytomegalovirus (CMV), but the remainder did not have abnormal fundus findings. Results. In all the optic nerves from A IDS patients With or without CMV retinitis, the vast majority of astro cytes stained strongly for TNF-alpha. Microglial cells (MPS-derived ma crophages) varied from not staining to staining strongly positive for TNF-alpha. However, oligodendrocytes were not labeled positively for T NF-alpha. Some endothelial cells also stained for TNF-alpha. Examinati on of normal optic nerves and controls did not reveal any cell type th at stained positively for TNF-alpha. Conclusions. The present study su pports the contention that TNF-alpha is a major mediator of AIDS-assoc iated optic neuropathy. HIV infection induces the production of TNF-al pha in macrophages and astrocytes, which probably causes demyelination and other neuronal damage.