| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
In comparison to the Lewis rat, in which 100% of animals innoculated with interphotoreceptor retinoid-binding protein (IRBP) and complete adjuvant develop experimental autoimmune uveoretinitis (EAU), the Brown Norway (BN) rat is relatively resistant. However, BN rats who have undergone renal cryotherapy have a high rate of EAU development. We set out to identify the pathogenic process and the common antigen involved in this particular type of EAU. (1) Using an anti-IRBP monoclonal antibody as a ligand, we extracted purified IRBP by affinity chromatography. This new method allowed us to avoid the problem of conventional Con A columns, in which the results are influenced by contamination by Con A itself. (2) In order to elucidate the pathogenic process of EAU, we studied the immune response to IRBP of splenic lymphocytes isolated from blood following IRBP innoculation. Lymphocytes isolated in the early period following innoculation displayed a proliferation response, and anti-IRBP antibo
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dy was identified on the 7th day following innoculation. In addition, antibodies against kidney and RPE were also identified at the same time. Thus we concluded that humoral immunity as well as cellular immunity were important for the development of this type of EAU. (3) Breakdown of the blood-retinal barrier (BRB) is necessary for the development of EAU, however there is a difference between the EAU normally produced by innoculation of Lewis rats and that produced by renal cyrotherapy in BN rats. While damage to the BRB in BN rats depends on antibody development against RPE, in Lewis rats the adhesion molecules ICAM-1 and LFA-1 are important to the breakdown of the BRB. (4) A serum antibody that reacts against ocular tissue, produced in response to renal antigen exposure, was found. (5) However, using an anti-IRBP monoclonal antibody as a ligand for affinity chromatography, we were unable to identify a common renal and ocular tissue antigen. We plan further studies using the antibody described in #4 above. Less
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