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(Investigative Ophthalmology and Visual Science. 2003;44:3374-3381.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0080
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Antigenic Specificity of Immunoprotective Therapeutic Vaccination for Glaucoma

Sharon Bakalash,1 Anat Kessler,2 Tal Mizrahi,1 Robert Nussenblatt,3 and Michal Schwartz1

1From the Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel; the 2Department of Ophthalmology, Ichilov Hospital, Tel Aviv, Israel; and the 3National Eye Institute, Bethesda, Maryland.

PURPOSE. To investigate the antigenic specificity of the immune neuroprotective mechanism that can protect retinal ganglion cells (RGCs) against death caused by high intraocular pressure (IOP).

METHODS. A unilateral increase in IOP was induced in rats by argon laser photocoagulation of the episcleral veins and limbal plexus. Rats with high IOP were immunized with glatiramer acetate (Cop-1, a synthetic copolymer) or with myelin-derived or uveitogenic peptides. When the steroid drug methylprednisolone was used, it was administered intraperitoneally every other day for 12 days.

RESULTS. Vaccination with myelin-derived peptides that reside in the axons failed to protect RGCs from death caused by high IOP. In contrast, IOP-induced RGC loss was reduced by vaccination with R16, a peptide derived from interphotoreceptor retinoid-binding protein, an immunodominant antigen residing in the eye. The benefit of protection against IOP-induced RGC loss outweighed the cost of the monophasic experimental autoimmune uveitis (EAU) that transiently developed in a susceptible rat strain. Treatment with methylprednisolone alleviated the disease symptoms, but caused further loss of RGCs. Cop-1 vaccination was effective in both EAU-resistant and EAU-susceptible strains.

CONCLUSIONS. To benefit damaged neurons, immune neuroprotection should be directed against immunodominant antigens that reside in the site of damage. In a rat model of high IOP, RGCs can benefit from vaccination with peptides derived from proteins that are immunodominant in the eye but not from myelin-associated proteins. This suggests that the site of primary degeneration in IOP-induced RGC loss is in the eye. Cop-1 vaccination apparently circumvents the site-specificity barrier and provides protection without risk of inducing autoimmune disease.




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