Retinal degeneration diseases and the visual retinoid cycle

视网膜变性疾病和视觉类维生素A循环

基本信息

批准号：
7679405
负责人：
Akiko Maeda
金额：
$ 8.1万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7679405
关键词：
Achievement Adolescent Affect Age related macular degeneration Animal Model Biochemical Biochemical Pathway Biological Blindness Cell Death Clinical Degenerative Disorder Developed Countries Developing Countries Disadvantaged Disease Disease model Elderly Electroretinography Evaluation Eye Goals Growth High Pressure Liquid Chromatography Human Individual Inherited Intracellular Transport Knowledge Lead Macular degeneration Medical Methods Modeling Molecular Mus Pathogenesis Patients Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phosphatidylethanolamine Phospholipids Photoreceptors Physical condensation Physiological Physiology Primates Production Research Research Personnel Retina Retinal Retinal Cone Retinal Degeneration Retinal Diseases Retinitis Pigmentosa Retinoids Safety Science Series Solutions Speed Stargardt&apos s disease Structure Techniques Therapeutic Vascular Endothelial Growth Factors Vision Visual Visual system structure base chromophore design drug candidate drug development effective therapy experience human disease in vivo Model inherited retinal degeneration inhibitor/antagonist insight liquid chromatography mass spectrometry novel phosphatidylethanolamine preclinical study programs retinal rods visual cycle

项目摘要

DESCRIPTION (provided by applicant): The specific aims of this proposal are to: 1) examine molecular mechanisms of retinal degenerative diseases using biochemical, molecular biological and physiological techniques; 2) establish retinal disease models of macular degeneration in mice; and 3) use these animal models to evaluate the safety and efficacy of pharmaceutical candidates for human drug development. Our achievements in series of studies with the visual retinoid cycle related retinal degenerative murine models leaded to discover novel disease causing mechanisms and to develop molecules that are strong candidates of treatment options for patients with retinal degenerations including inherited retinal degenerations and AMD (age-related macular degeneration), which is the leading cause of irreversible blindness in elderly people in developed countries, and which affects approximately 1.6 million individuals in the US. Recent ocular medical science succeeded in develop anti-CNV (choroidal neo-vasucularization) therapy with anti-VEGF (vascular endothelial growth factor) molecules for wet type AMD with CNV growth. However wet type AMD is only limited type of retinal diseases, and no treatment is available for the vast majority of patients who have dry form of AMD and other inherited retinal degenerative diseases. The molecules that we are studying show several beneficial effects on these incurable retinal diseases, and may become a first drug for them. Genetically modified mice will be employed for our study and rigorous evaluations including mechanisms, efficacy and safety of our candidate drugs by biochemical methods such as HPLC (high pressure liquid chromatography) and mass-spectrometry, and electroretinography, and histological/histocytochemical assessment. Molecular pathogenesis of dry type AMD and inherited retinal degeneration will be also examined with the murine models. My research based on my clinical experience is providing novel and important solutions for patients with currently incurable retinal degenerative diseases.

描述（由申请人提供）：该提案的具体目的是：1）使用生化，分子生物学和生理技术检查视网膜退行性疾病的分子机制； 2）建立小鼠黄斑变性的视网膜疾病模型； 3）使用这些动物模型来评估药物开发药物候选者的安全性和功效。我们在一系列研究中取得的成就与视觉性类动物相关的视网膜退化鼠模型导致发现了新型疾病，导致了机制，并发展分子，这些分子是为具有视网膜退化和AMD（包括年龄相关的黄斑变性）的视网膜变性和包括遗传性的个体的遗传性且盲目的人的最高效果的人的遗传性变性的患者的强有力的治疗选择，这是一位近似且属于Irvorvilsible的人，这是一代人，以及在典型的盲人中，且在一代人中，又是一代人，是一代人，又是一代人，是一年级的，又是一代人，是一代人，是一代人，是一代人，是一代人的一代人，是一代人的一代。我们。最近的眼科医学成功地开发了抗VEGF（血管内皮生长因子）分子的抗CNV（脉络膜新氧化剂）治疗，用于CNV生长。但是，湿型AMD仅是视网膜疾病类型的有限类型，对于患有AMD干燥和其他遗传性视网膜退行性疾病的绝大多数患者没有治疗。我们正在研究的分子对这些无法治愈的视网膜疾病显示出几种有益的作用，并可能成为它们的第一种药物。通过生物化学方法（例如HPLC（高压液体色谱）和质谱法计量学）以及电视图术以及组织学/组织化学化学评估，将采用转基因小鼠进行我们的研究和严格评估，包括机制，候选药物的功效和安全性。鼠模型还将检查干型AMD和遗传性视网膜变性的分子发病机理。我的基于临床经验的研究是为当前无法治愈的视网膜退行性疾病患者提供新颖的解决方案。