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

• 批准号: 10004055
• 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
• 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/10004055
• 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 environment; 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

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.

抽象的 新生血管形成在发达国家失明的主要原因中发挥着关键作用， 包括湿性年龄相关性黄斑变性（AMD）。在早期阶段，湿性 AMD 的特点是 分子变化。随后，脉络膜新生血管（CNV）发展，导致视网膜下出血， 疤痕和不可逆转的视力丧失。因此，在出血之前的早期阶段检测湿性 AMD 发育，可以改善视力。这项 K08 研究将开发和研究一种新型多模式分子 使用光声显微镜（PAM）、光学相干断层扫描（OCT）和 荧光显微镜可比目前使用分子技术更早地检测湿性 AMD 造影剂可在新血管形成中可视化 αvβ3 整合素。 CNV将本地化并量化至10以下 微米分辨率。这种实时的体内分子信息将允许有针对性的治疗和精确度 根据每位患者独特的分子表达量身定制的药物。 中心假设是 αvβ3 整合素的分子成像在早期诊断中具有敏感性和特异性。 脉络膜新生血管形成，因此可以用作早期检测脉络膜新生血管形成的生物标志物 黄斑变性。目标是：1）证明光声显微镜的安全性； 2） 使用 PAM、OCT 和荧光显微镜对 αvβ3 整合素进行多模式分子成像；和 3) 证明 αvβ3 整合素的分子成像可以更早地检测兔子模型中的 CNV。这 这项研究的两个具体目标是 1) 测试光声显微镜 (PAM) 可以安全地进行预测 可视化脉络膜视网膜微血管系统，以及 2) 量化使用金进行分子成像的程度 靶向 αvβ3 整合素的纳米颗粒定位于 CNV，并能够更早地观察 CNV。 该职业发展研究计划的长期目标是让研究者发展技能 以及高分辨率、多模式分子眼科成像方面的专业知识，以了解分子 导致脉络膜新生血管形成的机制。这将通过早期改善患者的护理 检测诊断、精准医学以及提高对基础生物学的理解。世界- 密歇根大学的著名导师和顾问都是各自领域的领导者， 完全致力于指导候选人发展成为一名独立调查临床医生科学家。