The concentration of myelin debris-like particles in the normal rat optic nerve

In the present study, we report that the concentration of myelin debris-like myelin basic protein-immunoreactive particles was observed in the distal (anterior)-most part of the myelinated region in the normal rat optic nerve. These particles were visualized using fluorescent immunohistochemistry with a mouse monoclonal anti-human myelin basic protein (MBPh) antibody (clone SMI-99). Fluorescent double immunohistochemistry, employing both the rat monoclonal anti-cow myelin basic protein (MBPc) antibody (clone 12) and the anti-MBPh antibody, revealed that the myelin basic protein immunoreactive-particles detected by the anti-MBPc antibody nearly completely overlapped with those immunostained by the anti-MBPh antibody. Since these antibodies target different sites, it can be concluded that these particles contain authentic myelin basic protein. We hypothesized that the MBPh-immunoreactive particles represent myelin debris-like structures in the normal rat optic nerve. Quantitative morphological analyses indicated that only 2 out of 6 differences in size and shape descriptors between the particles and the myelin debris observed in the damaged optic nerve of the glaucoma rat were statistically significant. Glial fibrillary acidic protein-immunoreactivity and glutamine synthetase-immunoreactivity were observed in the particles. Most of these particles were isolated from ionized calcium-binding adapter molecule 1-labeled microglia. These findings demonstrate that the myelin debris-like MBPh-immunoreactive particles are concentrated in the distal-most part of the myelinated region. This evidence suggests that the distal-most part is under physiologically stressed conditions. Furthermore, these findings may provide valuable insights into the pathophysiological mechanisms that induce localized vulnerability of the myelin sheaths.