Vaccination for neuroprotection in the mouse optic nerve: Implications foroptic neuropathies

T-cell autoimmunity to myelin basic protein was recently shown to be neurop rotective in injured rat optic nerves. In the present study, using the mous e optic nerve, we examined whether active immunization rather than passive transfer of T-cells can be beneficial in protecting retinal ganglion cells (RGCs) from post-traumatic death. Before severe crush injury of the optic n erve, SJL/J and C3H. SW mice were actively immunized with encephalitogenic or nonencephalitogenic peptides of proteolipid protein (PLP) or myelin olig odendrocyte glycoprotein (MOG), respectively. At different times after the injury, the numbers of surviving RGCs in both strains immunized with the no nencephalitogenic peptides pPLP 190-209 or pMOG 1-22 were significantly hig her than in injured controls treated with the non-self-antigen ovalbumin or with a peptide derived from beta -amyloid, a non-myelin-associated protein . Immunization with the encephalitogenic myelin peptide pPLP 139-151 was be neficial only when the disease it induced, experimental autoimmune encephal omyelitis, was mild. The results of this study show that survival of RGCs a fter axonal injury can be enhanced by vaccination with an appropriate self- antigen. Furthermore, the use of nonencephalitogenic myelin peptides for im munization apparently allows neuroprotection without incurring the risk of an autoimmune disease. Application of these findings might lead to a promis ing new approach for treating optic neuropathies such as glaucoma.