Calcium activated neutral proteinase (calpain) is an endopeptidase present
in the central nervous system which degrades myelin proteins. To examine th
e role of calpain in demyelination associated with optic neuritis, immunocy
tochemical expression of calpain was evaluated in Lewis rats with experimen
tal optic neuritis. Calpain expression was increased in activated microglia
, infiltrating macrophages, activated T cells, and reactive astrocytes in e
xperimental optic neuritis compared to controls. Calpain activity and trans
lational expression were also examined by Western blotting studies measurin
g the extent of myelin protein degradation, calpain-specific fodrin proteol
ysis, axonal neurofilament degradation, and calpain proenzyme content. Resu
lts showed myelin associated glycoprotein and 68 kD neurofilament protein l
evels were significantly decreased while calpain translational expression a
nd calpain-autolyzed fodrin levels were significantly increased in experime
ntal optic neuritis compared to controls. Thus, increased activity and tran
slational expression of calpain in optic neuritis may be integral to the pa
thogenesis of this disorder.