IN VIVO IMAGING IN AUTOIMMUNE UVEITIS

急性前葡萄膜炎(AAU)是人类最常见的眼内炎症形式，是一种眼部自身免疫性疾病。实验性自身免疫性前葡萄膜炎(EAAU)是AAU的一种啮齿动物模型。它是在Lewis大鼠体内通过对来自牛虹膜和睫状体的黑色素相关抗原(MAA)的致敏而产生的，并由CD4+T细胞介导。依赖于体外组织培养系统、组织的组织学分析或对牺牲动物的细胞/因子的分析，阻碍了体内免疫细胞的行为和功能。活体成像技术的最新进展使得具有高分辨率和信号灵敏度的小型化正电子发射断层扫描(PET)仪器的发展成为可能，用于小动物模型的应用。我们建议将放射科在PET扫描和正电子发射核苷酸生产方面的专业知识与眼科和视觉科学系在免疫学方面的专业知识结合起来，以研究EAAU的免疫发病机制。本提案的具体目标是：1.相关药用工具的设计、合成和评价。2.放射性核素标记抗体对免疫细胞功能及抗体与靶抗原结合的影响。3.免疫细胞在EAAU中的迁移和定位。

Acute anterior uveitis (AAU), the most common form of intraocular inflammation in man, is an autoimmune disease of the eye. Experimental autoimmune anterior uveitis (EAAU) is a rodent model of AAU. It is produced in the Lewis rat by sensitization to melanin associated antigen (MAA) derived from bovine iris and ciliary body and is mediated by CD4+ T cells. The behavior and function of immune cells in vivo has been hampered by reliance on in vitro tissue culture systems, histologic analysis of tissues or the analysis of cell/factors from sacrificed animals. Recent advances in in vivo imaging techniques has allowed the development of scaled down positron emission tomography (PET) instrumentation with high-resolution and signal sensitivity for application in small animal model. We propose to combine our expertise in PET scanning and the production of positron emitting nucleotides in the Department of Radiology with our expertise in immunology in the Department of Ophthalmology and Visual Sciences to study the immunopathogenesis of EAAU. The specific aims of this proposal are: 1. Design, synthesis and evaluation of relevant pharmaceutical tools. 2. Effect of radionuclide labeled antibodies on immune cell function and binding of the antibodies to their target antigens. 3. Immune cell migration and localization in EAAU.