Abstract
Abstract: :
Purpose:We investigated if vaccination with plasmid DNA coding for a retinal antigen can protect against EAU. Methods:B10.RIII mice were injected with a DNA fragment derived from human or murine IRBP and containing a major uveitogenic epitope (residues 161-180) in an expression vector using one of 2 protocols: 100 µg weekly of IRBP or vector DNA i.m. for 7 weeks, or 20 µg DNA weekly for 1-3 weeks by an i.v. hydrodynamics-based protocol (human IRBP only). All were challenged with a uveitogenic regimen of human IRBP peptide 161-180 two weeks after the last vaccination. EAU scores and immunologic responses were evaluated on day 21. Results:Both murine and human i.m. IRBP DNA protected mice from EAU, with the human being more protective. Protection in both groups correlated with decreased cellular proliferation. In the murine DNA group, protected vs. unprotected mice showed a trend towards increased IL-10 and decreased IFNγ production to the antigen. Mice vaccinated i.v. 1 to 3 times with the human DNA construct (the better tolerogen) were largely to completely protected. Conclusion:Vaccination with retinal DNA was effective in protecting against EAU and may be a useful approach to treating autoimmune retinal disease.
Keywords: 612 uveitis-clinical/animal model • 417 gene/expression • 327 autoimmune disease