Development of New Immunotherapy in Ophthalmology

目前的研究项目旨在开发新的眼科免疫疗法。为了治疗葡萄膜炎，在实验性自身免疫性葡萄膜炎模型中对各种免疫抑制剂进行了测试，发现环孢素（cyclosporine, CsA）在动物模型中对葡萄膜炎有较大的治疗能力。本品用于治疗白塞病合并难治性葡萄膜炎。共有69例白塞氏病耐药患者接受了CsA治疗。尽管CsA有一定的肾毒性，但新疗法抑制了疾病的眼部发作，视力预后比传统疗法好得多。并在动物模型上进行了CsC对葡萄膜炎的抑制实验，发现CsC对葡萄膜炎有明显的抑制作用，且肾毒性较低。为了治疗角膜移植排斥反应，建立了一种新的大鼠药物实验模型。采用不同MHC抗原的大鼠近交系进行穿透性角膜移植术。利用该模型对CsA的作用进行了分析。为治疗视网膜母细胞瘤，建立了视网膜母细胞瘤单克隆抗体。此外，用视网膜母细胞瘤细胞系Y-79细胞评价前列腺素的作用。PGD_2和J_2对视网膜母细胞瘤细胞均有抑制作用。一种针对视网膜母细胞瘤细胞系m-1131的单克隆抗体被发现对新鲜的人视网膜母细胞瘤有反应，但对其他人类肿瘤没有反应。

The present research project was aimed at developing new immunotherapies in opthalmology. For the treatment of uveitis, various immunosuppressants were tested in experimental autoimmune uveitis model and it was found that cyclosporine (CsA) had greate capacity to treat uveitis in the animal model. The agent was applied for the treatment of Behcet's disease with refractory uveitis. A total number of 69 patients with Behcet's disease who were resistant to conventional therapy were treated with CsA. The new therapy suppressed ocular attacks of the disease and the visual prognosis was much better than that of conventional hterapy, though CsA had some renal toxicity. CsC was also tested in animal model for its efficay in uveitis and it was found that CsC was effective to suppress uveitis in animals with much less renal toxicity. For the treatment of rejection of corneal transplantation, a new model for drug assay was established using rats. Penetrating keratoplasty was performed in inbred strains of rats having different MHC antigen. Using the model, the effects of CsA was assayed. For the treatment of retinoblastoma, monoclonal antibodies to retinobalstoma was established. Furthermore, effects of prostaglandins were eveluated using retinoblastoma cell line, Y-79 cells. PGD_2 and J_2 were found to have capacities to suppress retinoblastoma cells in vitro as well as in vivo. A monoclonal antibodies to retinoblastoma cell line, m-1131, was found to respond to fresh human retinoblastoma but not to other human tumors.