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Real-time In Vivo Visualization of the Molecular Processes in Choroidal Neovascularization

脉络膜新生血管形成分子过程的实时体内可视化

基本信息

批准号：
10237996
负责人：
Yannis Mantas Paulus
金额：
$ 22.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237996
关键词：
Age related macular degeneration Anatomy Angiography Animals Biological Markers Biological Models Biology Blindness Blood Vessels Burn injury Cell Death Choroidal Neovascularization Cicatrix Complex Contrast Media Deformity Detection Development Diagnosis Discipline Drusen Early Diagnosis Edema Electron Microscopy Electroretinography Endoglin Endothelial Cells Evaluation Fluorescein Fluorescein Angiography Fluorescence Fluorescence Microscopy Functional disorder Fundus photography Future Goals Grant Hemorrhage Histopathology Home Image Imaging Device Immunohistochemistry Individual Indocyanine Green Inflammation Integrin alphaVbeta3 KDR gene Knowledge Lasers Lateral Light Macular degeneration Maps Measures Mentors Methods Michigan Microscopy Modeling Molecular Molecular Biology Monitor Mus Ophthalmic examination and evaluation Ophthalmologist Optical Coherence Tomography Oryctolagus cuniculus Outcome Patient Care Patients Play Process Research Research Personnel Resolution Retina Retinal Diseases Role Rupture Safety Scientist Sensitivity and Specificity Signal Transduction System Testing Time Tissues Training Universities Vision Visual Visual Acuity Visualization Work career development cell injury contrast enhanced imaging modality imaging system improved in vivo individualized medicine intravenous administration molecular imaging multimodality nanoGold nanoparticle neovascularization novel polyacrylamide precision medicine research and development skills sound targeted treatment temporal measurement tool translational impact

项目摘要

ABSTRACT Neovascularization plays a pivotal role in the leading causes of blindness in the developed world, including wet age-related macular degeneration (AMD). At its early stage, wet AMD is characterized by molecular changes. Later, choroidal neovascularization (CNV) develops, leading to subretinal hemorrhage, scarring, and irreversible vision loss. Thus, detection of wet AMD at an earlier stage, before the hemorrhage develops, can improve vision. This K08 research will develop and investigate a novel multimodal molecular imaging system using photoacoustic microscopy (PAM), optical coherence tomography (OCT), and fluorescence microscopy to detect wet AMD at an earlier stage than currently possible using molecular contrast agents to visualize αvβ3 integrin in neovascularization. CNV will be localized and quantified to sub-10 micron resolution. This real-time, in vivo molecular information will allow for targeted treatment and precision medicine tailored to each patient’s unique molecular expression. The central hypothesis is molecular imaging of αvβ3 integrin will be sensitive and specific in early choroidal neovascularization and can thus be used as a biomarker in early detection of neovascularization in macular degeneration. The objectives are to: 1) demonstrate the safety of photoacoustic microscopy; 2) perform multimodal molecular imaging of αvβ3 integrin using PAM, OCT, and fluorescence microscopy; and 3) demonstrate that molecular imaging of αvβ3 integrin allows for earlier detection of CNV in rabbit models. The two specific aims of this study are 1) Test the prediction that photoacoustic microscopy (PAM) can safely visualize the chorioretinal microvasculature, and 2) Quantify the extent that molecular imaging using gold nanoparticles targeting αvβ3 integrin localize to CNV and enable earlier visualization of CNV. The long-term goals of this career development research plan is for the investigator to develop the skills and expertise in high resolution, multimodal molecular ophthalmic imaging to understand the molecular mechanisms leading to choroidal neovascularization. This will improve the care of patients through early detection diagnosis, precision medicine, and improved understanding of fundamental biology. The world- renowned mentors and advisors from the University of Michigan are leaders of their respective fields and are fully commited to guiding the candidate's development into an independent investigator clinician scientist.

摘要