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: 8126334
• 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/8126334
• 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）：该提案描述了一项为期5年的开发眼科研究职业的计划。我已经完成了博士后研究奖学金，随后进行了眼科/神经潮流学的居住和奖学金培训。现在，我将专注于通过部门间资源和指导的独特整合来扩展我的科学和研究技能。 职业发展活动将促进研究方法的指挥，以及眼睛的血管生物学和微生物学，适用于动脉粥样硬化和缺血性眼部疾病的机制。医学博士Steven L Bernstein和医学博士Charlene Hafer-Madco将指导我的科学发展。 Bernstein博士是非动脉前缺血性视神经神经病（NAION）研究的知名领导者，并开发了独特的啮齿动物光栓塞中风模型（RAION）。 Hafer-Macko博士对促血栓性疾病机制的主要研究兴趣与FHIS提案的重点有关。两位导师都培训了许多博士后研究员，研究生和居民。为了增强培训，该计划将获得备受推崇的医学科学家咨询委员会的专业知识。 研究将着重研究脂蛋白（a）（LP（a））和低密度脂蛋白（LDL）的作用，这是两种密切相关的过早动脉粥样硬化危险因素在缺血性眼部疾病中的作用。我将探讨LP（A）沉积与眼睛中的动脉粥样硬化的相关性以及LP（A）和LDL血清水平增加对缺血性视神经神经病的敏感性的影响。如果成功，证明脂蛋白血清水平升高，缺血性神经病和动脉粥样硬化之间的相关性可能会导致早期诊断和治疗动脉粥样硬化，以防止这种疾病的严重并发症。具体目的包括：1）在眼睛中定位和量化LP（a）沉积，2）建立一个体内模型，以分析增加血清LP（a）和LDL在缺血性视神经病中的影响。这将是对动脉粥样硬化眼病的这些特定机制的首次详细研究。 马里兰州大学通过为初级教职员工的发展提供了强大的机构支持，为拟议的职业发展奖（CDA）提供了理想的环境。该CDA将允许马里兰州大学为我提供必要的受保护时间，资源和培训，从而成功地从临床任命过渡到眼科研究的学术生涯。 相关性：拟议的研究基于以下假设：在眼中，类似于心脏和大脑，LP（A）和LDL促进动脉粥样硬化斑块的形成和炎症，从而导致血管内血栓形成和缺血性事件，例如缺血性神经性神经病。这些脂蛋白已被确定为动脉粥样硬化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的威胁生命疾病的新预防策略，并提供对眼科病病因的见解。