INCREASE OF MANGANESE SUPEROXIDE-DISMUTASE, BUT NOT OF CU ZN-SOD, IN EXPERIMENTAL OPTIC NEURITIS/

Purpose. To evaluate the role of manganese superoxide dismutase (MnSOD ) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protect ion of the optic nerve against the oxidative injury that contributes t o demyelination in experimental allergic encephalomyelitis (EAE). Meth ods. Immunocytochemistry for Mn-SOD and Cu/Zn-SOD and ultracytochemica l localization of hydrogen peroxide (H2O2) were performed on the optic nerves of guinea pigs with EAE and normal guinea pigs. Cell-specific enzyme expression of SOD was quantitated by computerized morphometric analysis. Results. Light microscopy showed a perivascular distribution of Mn-SOD-positive cells in the optic nerves of animals with EAE. Ele ctron microscopy showed that the Mn-SOD immunogold was confined exclus ively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the c ytoplasmic matrix and nucleus of cells of the optic nerve in both anim als with EAE and normal animals. Results of quantitative analysis of t he optic nerves of animals With EAE showed an 8-fold increase in Mn-SO D immunogold in astroglial cells and a 13-fold increase in microglial/ phagocytic cells in comparison with that of normal animals. Increases in MnSOD immunogold were contiguous to H2O2-derived reaction product. No increases in Cu/Zn-SOD immunogold were detected in EAE. Conclusions , Increases in Mn-SOD activity in astroglial cells and microglial/phag ocytic cells may contribute to the relative sparing of these cells fro m injury in EAE, whereas the low level of MnSOD in oligodendroglial ce lls and axons may increase their vulnerability to the effects of super oxide-induced oxidative injury that results in demyelination.