In Vivo Molecular Imaging of the Retina

视网膜体内分子成像

基本信息

批准号：
9266412
负责人：
JOHN S. PENN
金额：
$ 38.99万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9266412
关键词：
Address Adverse effects Animal Model Area Basic Science Biodistribution Biological Assay Biological Markers Blindness Blood Vessels Cell physiology Cells Choroidal Neovascularization Clinic Clinical Clinical Research Complication Computer Simulation Contrast Media Cultured Cells Densitometry Detection Diagnostic Disease Disease Progression Early Diagnosis Early treatment Elderly Endoglin Endothelial Cells Engineering Enzyme-Linked Immunosorbent Assay Exudative age-related macular degeneration Flow Cytometry Genetic Transcription Goals Gold Gold Colloid Healthcare Housekeeping Hybrids Hypoxia Image Imaging technology In Situ Hybridization In Vitro Inflammatory Injectable Intercellular adhesion molecule 1 Intravenous KDR gene Lasers Lead Lesion Mammalian Cell Mass Spectrum Analysis Measurement Messenger RNA MicroRNAs Molecular Molecular Profiling Molecular Target Mus Nanotechnology Noise Nucleic Acids Pathogenesis Pathology Patients Predisposition Proteins Publishing RNA RNA Sequences Research Retina Retinal Retinal Diseases Reverse Transcriptase Polymerase Chain Reaction Safety Signal Transduction Specificity Staging Structure Structure of retinal pigment epithelium Technology Testing Therapeutic Time Tissue imaging Tissues Transcript Translations Vascular Cell Adhesion Molecule-1 Vascular Diseases Vision Western Blotting Work base biomaterial compatibility clinical Diagnosis clinical translation contrast imaging drug discovery fluorescence imaging high resolution imaging imaging agent imaging biomarker imaging system improved in vivo in vivo optical imaging instrumentation knock-down locked nucleic acid member microRNA biomarkers molecular imaging molecular marker mouse model multidisciplinary nanoparticle neovascular neovascularization novel therapeutic intervention personalized medicine preclinical study protein expression public health relevance targeted imaging tool treatment response

项目摘要

DESCRIPTION (provided by applicant): Technologies for imaging the retina in animal models and patients have been significantly improved through advances in instrumentation, enabling high-resolution imaging of tissue structure. Furthermore, decades of basic and clinical research have identified a number of molecular biomarkers which may be valuable for assessing susceptibility to retinal disease, early disease, and disease progression, as well as dissecting molecular mechanisms in preclinical studies. The goal of this proposal is to build upon advances in imaging instrumentation and biomarker research in order to develop technologies for in vivo molecular imaging of the retina. The strategy is based on hairpin functionalized gold nanoparticles (hAuNP), biocompatible gold colloids engineered to enter living tissues and fluoresce upon hybridization with targeted messenger RNA (mRNA) or microRNA sequences. Recently published and preliminary studies demonstrate that hAuNP are capable of specifically targeting multiple distinct RNA sequences in mammalian cells and the retinal vasculature, without adverse effects on cell function. In this proposal, hAuNP will be utilized to validate mRNAs and microRNAs as biomarkers of choroidal neovascularization (CNV), using a mouse model of laser- induced choroidal neovascularization (LCNV). In Aim 1, hAuNP will be used to image CNV-relevant biomarkers in primary choroidal endothelial cells and retinal pigment epithelial cells, and the biodistribution and safety profiles of hAuNP will be further tested in mouse models. In Aims 2 and 3 of the proposal, hAuNP will be evaluated in a mouse model of LCNV in order to establish the utility of longitudinal, multiplexed RNA imaging. These studies will set the framework for molecular imaging of RNA and other molecular biomarkers in animal models, and will facilitate clinical translation of these technologies for early detection and staging of disease in patients.

描述（由申请人提供）：通过仪器的进步，动物模型和患者的视网膜成像技术已得到显着改进，从而实现了组织结构的高分辨率成像。此外，数十年的基础和临床研究已经确定了许多分子生物标志物，这些标志物对于评估视网膜疾病、早期疾病和疾病进展的易感性以及剖析临床前研究中的分子机制可能有价值。该提案的目标是利用成像仪器和生物标志物研究的进步来开发视网膜体内分子成像技术。该策略基于发夹功能化金纳米颗粒 (hAuNP)，这是一种生物相容性金胶体，经过工程改造，可以进入活体组织，并在与目标信使 RNA (mRNA) 或 microRNA 序列杂交时发出荧光。最近发表的初步研究表明，hAuNP 能够特异性靶向哺乳动物细胞和视网膜脉管系统中的多个不同的 RNA 序列，而不会对细胞功能产生不利影响。在该提案中，hAuNP 将使用激光诱导脉络膜新生血管 (LCNV) 小鼠模型来验证 mRNA 和 microRNA 作为脉络膜新生血管 (CNV) 生物标志物。在目标 1 中，hAuNP 将用于对原代脉络膜内皮细胞和视网膜色素上皮细胞中的 CNV 相关生物标志物进行成像，并将在小鼠模型中进一步测试 hAuNP 的生物分布和安全性。在该提案的目标 2 和 3 中，将在 LCNV 小鼠模型中评估 hAuNP，以建立纵向多重 RNA 成像的实用性。这些研究将为动物模型中 RNA 和其他分子生物标志物的分子成像奠定框架，并将促进这些技术的临床转化，以对患者的疾病进行早期检测和分期。