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The Journal of Neuroscience, January 1, 2001, 21(1):136-142
Vaccination for Neuroprotection in the Mouse Optic Nerve:
Implications for Optic Neuropathies
Jasmin
Fisher1,
Hanna
Levkovitch-Verbin1,
Hadas
Schori1,
Eti
Yoles1,
Oleg
Butovsky1,
Joel F.
Kaye2,
Avraham
Ben-Nun2, and
Michal
Schwartz1
Departments of 1 Neurobiology and
2 Immunology, The Weizmann Institute of Science, Rehovot,
Israel
T-cell autoimmunity to myelin basic protein was recently
shown to be neuroprotective in injured rat optic nerves. In the present study, using the mouse 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 nerve, SJL/J and C3H.SW mice
were actively immunized with encephalitogenic or nonencephalitogenic peptides of proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), respectively. At different times after the injury,
the numbers of surviving RGCs in both strains immunized with the
nonencephalitogenic peptides pPLP 190-209 or pMOG 1-22 were
significantly higher than in injured controls treated with the
non-self-antigen ovalbumin or with a peptide derived from -amyloid,
a non-myelin-associated protein. Immunization with the encephalitogenic
myelin peptide pPLP 139-151 was beneficial only when the disease it
induced, experimental autoimmune encephalomyelitis, was mild. The
results of this study show that survival of RGCs after axonal injury
can be enhanced by vaccination with an appropriate self-antigen.
Furthermore, the use of nonencephalitogenic myelin peptides for
immunization apparently allows neuroprotection without incurring the
risk of an autoimmune disease. Application of these findings might lead
to a promising new approach for treating optic neuropathies such as glaucoma.
Key words:
vaccination; neuroprotection; myelin; T-cells; CNS
injury; autoimmunity; optic nerve
Copyright © 2001 Society for Neuroscience 0270-6474/01/211136-07$05.00/0
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