Development of New Immunotherapy in Ophthalmology

本研究项目旨在开发眼科新的免疫疗法。在葡萄膜炎的治疗方面，通过实验性自身免疫性葡萄膜炎动物模型对多种免疫抑制剂进行了研究，发现环孢素A（CsA）对葡萄膜炎有较好的治疗作用。该制剂用于治疗白塞病合并难治性葡萄膜炎。共有69例白塞病患者对常规治疗耐药，用CsA治疗。新疗法抑制了该病的眼部发作，视力预后明显优于常规疗法，但CsA有一定的肾毒性。CsC还在葡萄膜炎动物模型中测试其功效，发现CsC在动物中有效抑制葡萄膜炎，且肾毒性小得多。为治疗角膜移植排斥反应，建立了一种新的大鼠角膜移植药物检测模型。在具有不同MHC抗原的近交系大鼠中进行穿透性角膜移植术。利用该模型，观察CsA对大鼠的作用。为了治疗视网膜母细胞瘤，建立了视网膜母细胞瘤的单克隆抗体。此外，使用视网膜母细胞瘤细胞系Y-79细胞来评价野牡丹素的作用。PGD_2和J_2在体内外均具有抑制视网膜母细胞瘤细胞的作用。一种抗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，但对其他人类肿瘤无反应。

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.