Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental optic neuritis.
OBJECTIVE
To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE).


METHODS
Immunocytochemistry for Mn-SOD and Cu/Zn-SOD and ultracytochemical 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. Electron microscopy showed that the Mn-SOD immunogold was confined exclusively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the cytoplasmic matrix and nucleus of cells of the optic nerve in both animals with EAE and normal animals. Results of quantitative analysis of the optic nerves of animals with EAE showed an 8-fold increase in Mn-SOD immunogold in astroglial cells and a 13-fold increase in microglial/phagocytic cells in comparison with that of normal animals. Increases in Mn-SOD 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/phagocytic cells may contribute to the relative sparing of these cells from injury in EAE, whereas the low level of Mn-SOD in oligodendroglial cells and axons may increase their vulnerability to the effects of superoxide-induced oxidative injury that results in demyelination.
Qi
X
X
Department of Ophthalmology, University of Florida, Gainesville 32610-0284, USA.
Guy
J
J
Nick
H
H
Valentine
J
J
Rao
N
N
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000378:metabolism; D009902:Optic Neuritis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010586:Phagocytes / Q000378:metabolism; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism*; D014018:Tissue Distribution
D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase