PRELIMINARY MORPHOMETRIC STUDY OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA)-INDUCED RABBIT OPTIC NEUROPATHY

Intravitreal injections of tumor necrosis factor-alpha (TNF alpha) ind uce 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 ey e model was conducted. Fifteen rabbits were injected in one eye only w ith TNF alpha (final doses: 2 U, 20 U and 200 U respectively), and opt ic nerve cross-sections were examined using a semi-automated image ana lysis system, at varying time intervals for up to 24 weeks post-inject ion. Control optic nerves (uninjected or injected with diluent only) w ere also assessed. Intact, degenerating and demyelinated axons were vi sible in TNF alpha-exposed optic nerves. Considerable variation was ob served 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 nerv es had significantly more degenerating profiles compared to control op tic nerves. These observations suggest a dose-dependent axonal loss an d degeneration associated with the morphological changes induced in ra bbit optic nerves following intravitreal injection of TNF alpha.