Neuroprotective Effects of the Cellular Prion Protein in Autoimmune Optic Neuritis

Although the pathologic role of the prion protein in transmissible spongiform encephalopathic diseases has been widely investigated, the physiologic role of the cellular prion protein (PrPC) is not known. Among the many functions attributed to PrPC, there is increasing evidence that it is involved in cell survival and mediates neuroprotection. A potential role in the immune response has also been suggested. However, how these two functions interplay in autoimmune disease is unclear. To address this, autoimmune optic neuritis, a model of multiple sclerosis, was induced in C57Bl/6 mice, and up-regulation of PrPC was observed throughout the disease course. In addition, compared with wild-type mice, in PrPC-deficient mice and mice overexpressing PrPC, histopathologic analysis demonstrated that optic neuritis was exacerbated, as indicated by axonal degeneration, inflammatory infiltration, and demyelination. However, significant neuroprotection of retinal ganglion cells, the axons of which form the optic nerve, was observed in mice that overexpressed PrPC. Conversely, mice lacking PrPC demonstrated significantly more neurodegeneration. This suggests that PrPC may have a neuroprotective function independent of its role in regulating the immune response.