The study of experimental autoimmune uveoretinitis in Brown Norway rats treated by renal cryosurgery

肾冷冻治疗棕色挪威大鼠实验性自身免疫性葡萄膜视网膜炎的研究

• 批准号: 03670837
• 负责人: SAKAI Jun-ichi
• 金额: $ 1.34万
• 依托单位: Tokyo Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670837/
• 关键词: Monoclonal antibody; Experimental autoimmune uveoretinitis; Interphotoreceptor retinoid-binding protein; Adhesion molecule; Blood-retinal barrier; Renal antigen; 合成ペプチド; モノクロ-ナル抗体

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 … More 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

与刘易斯大鼠相比，其中100%的动物接种感光细胞间类维生素A结合蛋白（IRBP）和完全佐剂发展实验性自身免疫性葡萄膜视网膜炎（EAU），布朗挪威（BN）大鼠是相对耐药。然而，接受肾冷冻治疗的BN大鼠具有高的EAU发展率。我们着手确定致病过程和共同抗原参与这种特殊类型的EAU。(1)以抗IRBP单克隆抗体为配体，通过亲和层析提取纯化的IRBP。这种新的方法使我们能够避免传统的Con A柱的问题，其中结果受到Con A本身污染的影响。(2)为了阐明EAU的发病过程，我们研究了从血液中分离的脾淋巴细胞接种IRBP后对IRBP的免疫应答。在接种后早期分离的淋巴细胞显示增殖反应，抗IRBP抗体和抗IRBP抗体在免疫后早期显示增殖反应。 ...更多信息 在接种后第7天鉴定出Dy。此外，还同时鉴定了抗肾抗体和抗RPE抗体。因此，我们得出结论，体液免疫以及细胞免疫是重要的发展，这种类型的EAU。(3)血-视网膜屏障（blood-retinal barrier，BRB）的破坏是EAU发生的必要条件，但刘易斯大鼠正常接种产生的EAU与BN大鼠肾冷冻治疗产生的EAU存在差异。虽然BN大鼠BRB的损伤取决于抗RPE抗体的产生，但在刘易斯大鼠中，粘附分子ICAM-1和LFA-1对BRB的破坏很重要。(4)发现了一种与眼组织反应的血清抗体，该抗体是在肾抗原暴露的反应中产生的。（5）然而，使用抗IRBP单克隆抗体作为亲和层析的配体，我们无法鉴定共同的肾和眼组织抗原。我们计划使用上述#4中描述的抗体进行进一步研究。少