Tumor necrosis factor-alpha (TNF-α)-induced optic neuropathy in rabbits

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Abstract
Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNFoc) in various demyelinating diseases/ including HIV-related encephalopathy. To investigate whether intravitreal TNFoc can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNFoc (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNFa-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNFoc-exposed optic nerves> and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNFoc-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNFoc- exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNFoc on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in generaland optic nerve degeneration in particular; has been described in AIDS, and TNFoc levels may be elevated in this disease, it is of great clinical significance that TNFoc has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNFoc can be pursued for treatment for the neurological symptoms of AIDS. [Neurol Res 1996; 18: 176–184]

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