RECOVERIN - A POTENT UVEITOGEN FOR THE INDUCTION OF PHOTORECEPTOR DEGENERATION IN LEWIS RATS
RECOVERIN - A POTENT UVEITOGEN FOR THE INDUCTION OF PHOTORECEPTOR DEGENERATION IN LEWIS RATS
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DOI：
10.1006/exer.1994.1130
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发表时间：
1994-10-01
影响因子：
3.4
通讯作者：
POLANS, A
中科院分区：
文献类型：
--
作者：
ADAMUS, G;ORTEGA, H;POLANS, A
Recovery是一种钙结合蛋白，被鉴定为人类视网膜的副肿瘤变性疾病（称为癌症相关视网膜病变（CAR））中的自身抗原。在本研究中，我们研究了恢复素是否可以引起导致视网膜感光细胞变性的免疫反应，以及是否可以建立CAR的动物模型，用恢复素注射刘易斯大鼠引起感光细胞变性，观察到葡萄膜视网膜炎的几个特征，包括玻璃体细胞，血管周围炎，视网膜病变和感光细胞层的完全丧失。在免疫后10-14天观察到视网膜炎症的第一临床体征。视网膜最早的组织学变化也出现在免疫后14天。经常观察到淋巴细胞和一些多形核细胞浸润感光细胞层和视网膜内层。光感受器受损，后来完全退化。该事件序列与所有试验动物中的高抗恢复蛋白抗体滴度相关。免疫后第7天至第28天测定的细胞对恢复素的反应显示出对恢复素的强体外增殖活性。此外，所有方面的退行性事件可以再现在幼稚的动物通过过继转移的刺激淋巴细胞从动物先前免疫与recoverin。这项研究表明，成功诱导光感受器变性使用recoverin作为免疫原。我们证明，恢复是一个有效的抗原和葡萄膜炎原。这些观察结果可能与我们对人类汽车的理解有关。
Recoverin is a calcium-binding protein identified as an autoantigen in a paraneoplastic degenerative disease of the human retina known as cancer-associated retinopathy (CAR). In this study we investigated whether recoverin could elicit an immune response leading to the degeneration of photoreceptor cells in a rodent retina, and whether an animal model of CAR could be developed.Injection of Lewis rats with recoverin caused degeneration of the photoreceptor cells, Several features of uveoretinitis were observed, including vitreous cells, perivasculitis, retinal lesions and complete loss of the photoreceptor cell layer. The first clinical signs of retinal inflammation were observed 10-14 days after immunization. The earliest histological changes in the retina also were observed 14 days after immunization. Infiltration of the photoreceptor cell layer and inner layers of the retina with lymphocytic and some polymorphonuclear cells was frequently observed. Photoreceptors were damaged and later fully degenerated. This sequence of events was associated with high antibody titers against recoverin in all animals tested. Cellular responses to recoverin assayed between days 7 and 28 after immunization showed strong in vitro proliferative activities to recoverin. In addition, all aspects of the degenerative events could be reproduced in naive animals by the adoptive transfer of stimulated lymphocytes obtained from animals previously immunized with recoverin.This study demonstrates the successful induction of photoreceptor degeneration using recoverin as an immunogen. We demonstrate that recoverin is both a potent antigen and uveitogen. These observations may be relevant to our understanding of CARs in humans.