Preliminary morphometric study of tumor necrosis factor-alpha (TNF alpha)-induced rabbit optic neuropathy.

Abstract

Intravitreal injections of tumor necrosis factor-alpha (TNF alpha) induce morphological changes in the optic nerve suggesting a primary TNF alpha-induced optic neuropathy. A preliminary morphometric analysis of axonal loss and degeneration in optic nerves of a TNF alpha rabbit eye model was conducted. Fifteen rabbits were injected in one eye only with TNF alpha (final doses: 2 U, 20 U and 200 U respectively), and optic nerve cross-sections were examined using a semi-automated image analysis system, at varying time intervals for up to 24 weeks post-injection. Control optic nerves (uninjected or injected with diluent only) were also assessed. Intact, degenerating and demyelinated axons were visible in TNF alpha-exposed optic nerves. Considerable variation was observed between TNF alpha-exposed optic nerves, however the intact axon density consistently decreased in the 200 U TNF alpha group, although not in the 2 U and 20 U groups. Overall, TNF alpha-exposed optic nerves had significantly more degenerating profiles compared to control optic nerves. These observations suggest a dose-dependent axonal loss and degeneration associated with the morphological changes induced in rabbit optic nerves following intravitreal injection of TNF alpha.