LIPOPROTEIN (A) IN VASCULAR DISEASES OF THE EYE

脂蛋白 (A) 在眼部血管疾病中的作用

• 批准号: 8320990
• 负责人: MICHAELA K MATHEWS
• 金额: $ 17.93万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320990
• 关键词: Address; Advisory Committees; Affect; Age; Age related macular degeneration; Age-Months; Animal Model; Animals; Anterior Ischemic Optic Neuropathy; Appointment; Arterial Fatty Streak; Atherosclerosis; Biological Assay; Biology; Blood Vessels; Brain; Caliber; Cell Adhesion Molecules; Cells; Cerebrum; Choroid; Clinical; Coronary artery; Deposition; Development; Diagnosis; Diet; Disease; Doctor of Philosophy; Dropout; Early Diagnosis; Early treatment; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Enzymes; Etiology; Event; Exhibits; Eye; Eye diseases; Faculty; Fatty acid glycerol esters; Fellowship; Future; Heart; Heart Diseases; Human; Image Analysis; Immunosorbents; India ink stain; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Investigation; Ischemia; Ischemic Optic Neuropathy; K-Series Research Career Programs; Knockout Mice; Lead; Life; Link; Lipoprotein (a); Lipoproteins; Location; Low Density Lipoprotein Receptor; Low-Density Lipoproteins; Maryland; Measures; Medical; Mentors; Mentorship; Microbiology; Modeling; Mus; Myocardial Infarction; Nature; Nerve; Neuronal Injury; Neurons; Ophthalmology; Optic Nerve; Perception; Perfusion; Plasminogen; Play; Postdoctoral Fellow; Predisposition; Prevention strategy; Principal Investigator; Process; Program Development; Propidium Diiodide; Reaction; Relative (related person); Research; Research Methodology; Residencies; Resources; Retina; Risk; Risk Factors; Rodent; Rodent Model; Role; Scientist; Serum; Severities; Smooth Muscle Actin Staining Method; Smooth Muscle Myocytes; Stroke; Thrombosis; Time; Training; Training Programs; Transgenic Mice; Universities; Vascular Diseases; Work; apolipoprotein Lp(a+); base; career; career development; cell injury; choroidal artery; clinically relevant; density; design; eye blood vessel; feeding; graduate student; in vivo; in vivo Model; inflammatory marker; insight; interest; macrophage; member; oil red O; premature atherosclerosis; prevent; programs; research study; skills; theories

DESCRIPTION (provided by applicant): This proposal describes a 5 year program for the development of an academic research career in Ophthalmology. I have completed a postdoctoral research fellowship, followed by residency and fellowship training in Ophthalmology/ Neuroophthalmology. Now I will focus upon expanding my scientific and research skills through a unique integration of interdepartmental resources and mentorship. Career development activities will promote the command of research methodology, as well as vascular biology and microbiology of the eye, as applied to mechanisms of atherosclerotic and ischemic eye disease. Steven L Bernstein, MD, PhD and Charlene Hafer-Madco, MD will mentor my scientific development. Dr. Bernstein is a renowned leader in the research of nonarteritic anterior ischemic optic neuropathy (NAION), and has developed a unique rodent photoembolic stroke model (rAION). Dr. Hafer-Macko's primary research interest in prothrombotic disease mechanisms relate to the focus of fhis proposal. Both mentors have trained numerous postdoctoral fellows, graduate students and residents. To enhance the training, the program will enlist the expertise of an advisory committee of highly regarded medical scientists. Research will focus on investigating the role of Lipoprotein(a) (Lp(a)) and Low-density lipoprotein (LDL), two closely related, well-defined risk factors of premature atherosclerosis, in ischemic eye disease. I will explore the correlation of Lp(a) deposition with atherosclerosis in the eye and the effect of increased Lp(a) and LDL serum levels on susceptibility to ischemic optic neuropathy. If successful, proving a correlation between elevated lipoprotein serum levels, ischemic optic neuropathy and atherosclerosis may lead to earlier diagnosis and treatment of atherosclerosis to prevent severe complications of this disease. Specific aims include: 1) Localizing and quantifying Lp(a) deposition in the eye, 2) Establishing an in vivo model for the analysis of the effect of increased serum Lp(a) and LDL in ischemic optic neuropathy. This will be the first detailed investigation into these specific mechanisms of atherosclerotic eye disease. The University of Maryland provides an ideal setting for the proposed career development award (CDA) by providing strong institutional support for the development of junior faculty members into independent scientists. This CDA will allow the University of Maryland to provide me with the necessary protected time, resources, and training to successfully transition from a clinical appointment into an academic career in ophthalmology research. RELEVANCE: The proposed research is based on the hypothesis that in the eye, similar to the heart and brain, Lp(a) and LDL promote atherosclerotic plaque formation and inflammation, leading to intravascular thrombosis and ischemic events, such as ischemic optic neuropathy. These lipoproteins are well established as risk factors for atherosclerotic heart disease and stroke. Therefore, establishing a correlation between Lp(a), LDL and ocular ischemia may lead to new prevention strategies for atherosclerosis and associated life-threatening diseases as well as provide insight into the etiology of ophthalmic disease.

描述（由申请人提供）：该提案描述了一个为期 5 年的眼科学术研究职业发展计划。我已经完成了博士后研究奖学金，随后接受了眼科/神经眼科的住院医师培训和奖学金培训。现在，我将专注于通过跨部门资源和指导的独特整合来扩展我的科学研究技能。 职业发展活动将促进对研究方法以及眼睛血管生物学和微生物学的掌握，应用于动脉粥样硬化和缺血性眼病的机制。 Steven L Bernstein 博士和 Charlene Hafer-Madco 医学博士将指导我的科学发展。 Bernstein 博士是非动脉炎性前部缺血性视神经病变 (NAION) 研究领域的著名领导者，并开发了一种独特的啮齿动物光栓塞中风模型 (rAION)。 Hafer-Macko 博士对血栓性疾病机制的主要研究兴趣与该提案的重点相关。两位导师都培养了众多博士后、研究生和住院医师。为了加强培训，该计划将招募由备受尊敬的医学科学家组成的咨询委员会的专业知识。 研究重点是调查脂蛋白(a) (Lp(a)) 和低密度脂蛋白(LDL) 在缺血性眼病中的作用，这两个密切相关且明确的过早动脉粥样硬化风险因素。我将探讨 Lp(a) 沉积与眼部动脉粥样硬化的相关性，以及 Lp(a) 和 LDL 血清水平升高对缺血性视神经病变易感性的影响。如果成功，证明脂蛋白血清水平升高、缺血性视神经病变和动脉粥样硬化之间的相关性可能会导致动脉粥样硬化的早期诊断和治疗，以预防该疾病的严重并发症。具体目标包括：1) 定位和量化 Lp(a) 在眼中的沉积，2) 建立体内模型来分析血清 Lp(a) 和 LDL 增加对缺血性视神经病变的影响。这将是对动脉粥样硬化性眼病这些具体机制的首次详细研究。 马里兰大学为初级教员发展成为独立科学家提供强有力的机构支持，为拟议的职业发展奖（CDA）提供了理想的环境。该 CDA 将使马里兰大学能够为我提供必要的受保护时间、资源和培训，以成功地从临床任命过渡到眼科研究的学术职业。 相关性：拟议的研究基于这样的假设：在眼睛中，与心脏和大脑类似，Lp​​(a) 和 LDL 会促进动脉粥样硬化斑块形成和炎症，导致血管内血栓形成和缺血性事件，例如缺血性视神经病变。这些脂蛋白已被确定为动脉粥样硬化性心脏病和中风的危险因素。因此，建立 Lp(a)、LDL 和眼部缺血之间的相关性可能会导致动脉粥样硬化和相关危及生命的疾病的新预防策略，并深入了解眼科疾病的病因学。