In
AIDS patients, axonal degeneration in the optic nerve occurs as a histopathological manifestation of the
optic neuropathy. Direct
infection of neurons by HIV is unlikely, and the axonal injury may be an indirect effect mediated by cytotoxic factors such as
tumor necrosis factor-alpha (
TNF-alpha) which we have previously demonstrated to cause axonal degeneration in the rabbit optic nerve. To test the suppressive effects of
pentoxifylline in preventing
TNF-alpha-mediated axonal degeneration, we applied
pentoxifylline to an established rabbit model that demonstrates an
AIDS-like
optic neuropathy using intravitreal
TNF-alpha injections. Degenerated axonal profiles were numerous in control rabbit optic nerve (mean 1879) and reduced in rabbits receiving the medium dose of
pentoxifylline (300 mg PO BID, mean 439, p < 0.001) and the highest dose of
pentoxifylline (600 mg PO BID, mean 120, p < 0.007). High dose
pentoxifylline reduced
TNF-alpha-induced axonal losses to less than 10% that seen without
pentoxifylline pretreatment. Lower doses of
pentoxifylline had a lesser but significant protective effect. Our results suggest that
TNF-alpha-mediated axonal degeneration can be suppressed by high doses of
pentoxifylline.
Pentoxifylline may therefore be useful in
AIDS patients demonstrating neurological or neuro-ophthalmological symptoms.