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令人眼花疾病，是美国人失明的主要原因。特征自身免疫性疾病的复发和减轻靶组织的炎症。如果是自身免疫性葡萄膜炎，眼睛是目标，因为眼睛允许通过大部分器官渗透光，所以研究眼睛中的免疫反应具有特殊的优势。这个优点是光可以用作无创的标记注射过程中存在的细胞并随着注射消退而迁移的方法。实验自身免疫性葡萄膜炎（EAU）是自身免疫性葡萄膜炎的最广泛使用的模型。我们建议生成和验证稳定表达光诱导表达系统的新型小鼠，该系统可用于在任何过程中用来标记眼睛中的细胞在EAU之前或期间（特定目标1）。我们的假设是一种表达光活化的转基因小鼠 CRE将是永久标记眼睛中细胞的绝佳工具。目前，唯一可用的长期标签系统依靠注射可以有毒并从靶组织中扩散出来的化合物。该提议利用一本小说可驱动CRE激活诱导永久性遗传变化的光活化系统，允许永久标记目标细胞。在哺乳动物细胞系中已证明了第二代系统，在小鼠中已通过转染目标细胞。在此提案中，我们将生成一条新颖的鼠标线，稳定地表达了回答与器官相关的免疫问题的目的，该问题易于通过光线通过。重要的是，这将允许许多未来的研究，这些研究可以通过在任何细胞的非侵入性标记来解决在任何组织中都可以渗透光。