Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats

Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats
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DOI:
10.1006/exer.2000.0893
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发表时间:
2000-10-01
影响因子:
3.4
通讯作者:
Sakuragi, S
Sakuragi, S
中科院分区:
医学3区
文献类型:
--
作者:
Yamaki, K;Kondo, I;Sakuragi, S

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Vogt-Koyanagi-Harada(VKH)病是一种眼部炎症性疾病,被认为是一种针对黑素细胞的细胞介导的自身免疫性疾病。要了解更多关于VKH疾病的机制,识别疾病特异性抗原和动物模型的开发至关重要。我们表达并纯化了黑素细胞特异性蛋白酪氨酸酶相关蛋白1(TRP 1)和2(TRP 2)。刘易斯大鼠在用TRP 1或TRP 2免疫后12天发生眼和眼外炎性疾病,其临床特征在于炎性细胞的浸润和大量纤维蛋白在眼睛的前房和后房中的积累。组织学上,前房、后房、虹膜、睫状体、脉络膜、视网膜下腔和玻璃体内均可见炎性细胞。在严重的情况下,观察到视网膜的浆液性脱离。在轻度病例中,观察到被正常脉络膜视网膜结构包围的局灶性炎性病变,并且在注射后炎症持续超过42天。有些眼睛显示脉络膜或视网膜色素上皮中的上皮样细胞积聚,这与VKH病患者中发现的Dalen-Fuchs结节相似。光感受器外节和外核层的改变不太严重,比视网膜抗原诱导的实验性自身免疫性葡萄膜炎。还观察到眼外表现,如皮肤病变和脑膜炎。这些大鼠的临床病程和组织学结果与VKH病患者的变化相似。(C)北京大学出版社.
Vogt-Koyanagi-Harada (VKH) disease is an ocular inflammatory disease and is considered to be a cell-mediated, autoimmune disease against melanocytes. To learn more about the mechanisms involved in VKH disease, the identification of the antigens specific to the disease and the development of an animal model are critically important. We have expressed and purified the melanocyte specific proteins, tyrosinase-related protein 1 (TRP1) and 2 (TRP2). Lewis rats developed an ocular and extraocular inflammatory disease 12 days after immunization with TRP1 or TRP2 that was characterized clinically by the infiltration of inflammatory cells and accumulation of massive fibrin in the anterior and posterior chambers of the eye. Histologically, inflammatory cells were found in the anterior and posterior chambers, iris, ciliary body, the choroid, subretinal space and Vitreous body. In severe cases, a serous detachment of the retina was observed. In mild cases, focal inflammatory lesions surrounded by normal chorioretinal architecture were observed and the inflammation persisted for more than 42 days after the injection. Some eyes showed accumulation of epithelioid cells in the choroid or the retinal pigment epithelium which were similar to the Dalen-Fuchs nodules found in patients with VKH disease. The alterations of the photoreceptor outer segment and the outer nuclear layer were less severe than in experimental autoimmune uveitis induced by retinal antigens. Extraocular manifestations such as skin lesions and meningitis were also observed. The clinical course and histological findings in these rats resembled the changes in patients with VKH disease. (C) 2000 Academic Press.