Dynamics of the Ocular Immune Response During Uveitis

葡萄膜炎期间眼部免疫反应的动态

基本信息

批准号：
9919552
负责人：
Darren James Lee
金额：
$ 18.76万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9919552
关键词：
Address Adrenal Cortex Hormones Affect American Antigen-Presenting Cells Arabidopsis Area Autoantigens Autoimmune Diseases Autoimmune Process Blindness Cell Line Cells Characteristics Cornea Development Diffuse Discipline Disease Disease remission Enterobacteria phage P1 Cre recombinase Experimental Models Eye Future Gene Expression Gene Silencing Generations Genetic Goals Human Immune Immune response Immunobiology Immunologics Immunology Inflammation Inflammatory Injections Label Lead Light Lighting Lymphocyte Mammalian Cell Mediating Methods Modeling Mus Mutation Neurologic Neurons Organ Patients Penetration Phase Photoreceptors Regulatory T-Lymphocyte Relapse Research Personnel Research Priority Resistance Resolution Resources Retina Scientist Spleen Steroids Suppressor-Effector T-Lymphocytes System T cell response Technology Therapeutic immunosuppression Time Tissues Transgenes Transgenic Mice Treatment Failure United States Uveitis Vision Vision research autoimmune uveitis base dimer in vivo inducible gene expression lens mouse model novel novel strategies novel therapeutics response success tool trafficking uveoretinitis

项目摘要

Abstract Uveitis is a potentially blinding disease’s that are a leading cause of blindness among Americans. Characteristic of autoimmune diseases is marked relapsing and remitting inflammation of the target tissue. In the case of autoimmune uveitis, the eye is the target and because the eye allows for the penetration of light through much of the organ, study of the immune response in the eye has a particular advantage. This advantage being that light could be used as a non-invasive method to label cells that are present during inflammation and migrate out as the inflammation resolves. Experimental autoimmune uveitis (EAU) is the most widely used model of autoimmune uveitis. We propose to generate and validate a novel mouse that stably expresses a light inducible expression system that can be used to label cells in the eye during any point before or during EAU (Specific Aim 1). Our hypothesis is that a transgenic mouse that expresses photoactivatable Cre will be an excellent tool to permanently label cells in the eye. Currently, the only long-term labeling systems available rely on the injection of compounds that can be toxic and diffuse out of the target tissue. This proposal utilizes a novel photoactivatable system that drives Cre activation to induce permanent genetic changes that allow for permanent labeling of the target cells. A second-generation system has been demonstrated in mammalian cell lines, and in mice by transfecting the target cells. In this proposal we will generate a novel mouse line that stably expresses the transgenes for the purpose of answering the immunological questions that relate to an organ that readily allows for light to pass through. Importantly, this will allow for many future studies that can be answered through a non-invasive labeling of cells at any time in any tissue that allows for the penetration of light.

抽象的葡萄膜炎是一种潜在的致盲疾病，是美国人失明的主要原因。自身免疫性疾病的特征是靶组织炎症明显复发和缓解。葡萄膜炎，眼睛是目标，因为眼睛允许光线穿透大部分器官，因此研究眼睛的免疫反应具有特殊的优势，即光可以用作非侵入性的。标记炎症期间存在的细胞并在炎症消退时迁移出去的方法。自身免疫性葡萄膜炎（EAU）是最广泛使用的自身免疫性葡萄膜炎模型。我们建议生成并验证一个模型。稳定表达光诱导表达系统的新型小鼠，可用于在任何过程中标记眼睛中的细胞 EAU 之前或期间的点（具体目标 1）我们的假设是表达光激活的转基因小鼠。 Cre 将成为永久标记眼睛细胞的绝佳工具，是目前唯一可用的长期标记系统。依赖于注射有毒化合物并扩散出目标组织。该提案利用了一种新颖的方法。光激活系统可驱动 Cre 激活以诱导永久性基因变化，从而实现永久性标记靶细胞的第二代系统已在哺乳动物细胞系和小鼠中得到证实。在本提案中，我们将生成一种稳定表达转基因的新型小鼠品系。目的是回答与容易让光通过的器官相关的免疫学问题。重要的是，这将允许许多未来的研究可以通过在任何时间对细胞进行非侵入性标记来回答。在任何允许光穿透的组织中的时间。