Caspi R R, Roberge F G, Chan C C, Wiggert B, Chader G J, Rozenszajn L A, Lando Z, Nussenblatt R B
Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892.
J Immunol. 1988 Mar 1;140(5):1490-5.
Experimental autoimmune uveoretinitis (EAU) is an organ-specific, T lymphocyte-mediated autoimmune disease, which serves as a model for several human ocular inflammations of an apparently autoimmune nature. EAU pathology in some rodents and in monkeys can readily be induced by immunization with several different retinal proteins; however, advancing research into the cellular mechanisms of this disease has raised the need for an EAU model in an immunologically and genetically well defined species. We report here the induction of EAU in the mouse, which has hitherto been considered a species refractory to EAU, with two retinal Ag, the retinal soluble Ag and the interphotoreceptor retinoid-binding protein. Although all the mouse strains tested exhibited lymphocyte responses and antibody titers to both retinal Ag, EAU was inducible in only some of the strains, and the uveitogenic responses to retinal soluble Ag and interphotoreceptor retinoid-binding protein appeared to be mutually exclusive. The EAU model in mice was found to differ in several respects from the EAU model in other rodent species. Induction of the disease was achieved with a relatively high dose of Ag and an intensified immunization protocol, and the onset of disease was later, the duration was longer, and the course was less acute. Anterior segment involvement was slight or nonexistent, and damage to the retina and uvea was of a focal rather than of a diffuse nature. Murine EAU appeared to approximate some types of human uveitis more closely than the EAU models described in other rodent species with respect to its pathologic manifestations as well as its more chronic course. The relatively longer duration of the active stage of disease in murine EAU should facilitate therapeutic intervention in established disease, which was not feasible in the more acute models of EAU. The extensive knowledge of the immunologic parameters of the mouse and the availability of genetically defined strains should be of great value in the study of cellular mechanisms and immunogenetics of ocular autoimmune disease.
实验性自身免疫性葡萄膜视网膜炎（EAU）是一种器官特异性、T淋巴细胞介导的自身免疫性疾病，可作为几种明显具有自身免疫性质的人类眼部炎症的模型。在一些啮齿动物和猴子中，用几种不同的视网膜蛋白进行免疫接种可很容易地诱发EAU病理改变；然而，随着对该疾病细胞机制研究的不断深入，人们越来越需要在免疫和遗传背景明确的物种中建立EAU模型。我们在此报告了用两种视网膜抗原，即视网膜可溶性抗原和光感受器间类视黄醇结合蛋白，在小鼠中诱导出EAU，而小鼠迄今一直被认为是对EAU具有抗性的物种。尽管所有测试的小鼠品系对两种视网膜抗原均表现出淋巴细胞反应和抗体滴度，但仅在部分品系中可诱导出EAU，并且对视网膜可溶性抗原和光感受器间类视黄醇结合蛋白的葡萄膜致病反应似乎相互排斥。发现小鼠的EAU模型在几个方面与其他啮齿动物物种的EAU模型不同。该疾病的诱导需要相对高剂量的抗原和强化的免疫方案，且疾病发作较晚，持续时间较长，病程也不那么急性。眼前节受累轻微或不存在，视网膜和葡萄膜的损伤呈局灶性而非弥漫性。就其病理表现以及更慢性的病程而言，小鼠EAU似乎比其他啮齿动物物种中描述的EAU模型更接近某些类型的人类葡萄膜炎。小鼠EAU疾病活动期相对较长的持续时间应有助于对已确诊疾病进行治疗干预，而这在更急性的EAU模型中是不可行的。小鼠免疫参数的广泛知识以及基因定义品系的可得性在眼部自身免疫性疾病的细胞机制和免疫遗传学研究中应具有重要价值。
