Choroidal Disease Mechanisms in AMD

AMD 的脉络膜疾病机制

• 批准号: 9078550
• 负责人: Elliott H Sohn
• 金额: $ 38.03万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9078550
• 关键词: Ablation; Age; Age related macular degeneration; Anatomy; Animal Model; Appearance; Architecture; Atrophic; Beavers; Biochemical; Biochemical Pathway; Biochemistry; Biological; Biology; Blindness; Blood Vessels; Bruch' s basal membrane structure; Candidate Disease Gene; Cathepsins; Cellularity; Choroid; Choroid Diseases; Collection; Complex; Data; Disease; Dropout; Eye; Fibrosis; Functional disorder; Genes; Genetic; Histology; Human; Image; Iowa; Laboratories; Laboratory Scientists; Lead; Life; Metalloproteases; Modality; Molecular; Molecular Biology; Molecular Genetics; Optical Coherence Tomography; Pathogenesis; Pathway interactions; Patients; Phenotype; Photoreceptors; Play; Research; Research Personnel; Retina; Retinal; Role; Structure; Structure of retinal pigment epithelium; Testing; Thick; Tissues; Vascular System; Vascular blood supply; Vision; Western World; base; cohort; disorder of macula of retina; experience; geographic atrophy; image processing; in vivo; insight; macula; multidisciplinary; next generation; next generation sequencing; normal aging; novel; novel therapeutics; programs; public health relevance; research study; tool; translational study

 DESCRIPTION (provided by applicant): We propose to investigate the pathophysiology of choroidal degeneration in age-related macular degeneration (AMD), the most common form of untreatable central vision loss in the western world. The choroid, the complex vascular system supplying the outer retina, photoreceptors, and retinal pigment epithelium (RPE), can now be visualized in living humans using enhanced depth imaging optical coherence tomography (OCT). Recent studies of the choroid by clinicians using OCT, and by laboratory scientists using donor eyes, suggest the choroid is a critical tissue in the pathogenesis AMD, especially as it relates to degeneration of the RPE in geographic atrophy. Access to patients with AMD (from Iowa and from large, multicenter eye studies), a large human donor eye collection, extensive experience in histology, molecular biology, genetics, and image processing/analysis, and state-of-the-art genetics and molecular biology laboratories will provide us with a unique opportunity to uncover the critical role of the choroid in AMD. We will use human donor eyes to determine the biochemical pathways and anatomical differences occurring in eyes with AMD. This will allow us to explore the anatomic details of choroidal loss and determine the molecular basis of changes in thin choroids and eyes with AMD. We will also explore the consequences of choroidal loss on the retina in novel animal models. Finally, we will leverage our extensive experience in genetics to evaluate the extent to which genes already implicated in AMD also form the basis for choroidal degeneration using very large patient cohorts. This project also has the prospect of discovering new genes that impact structural features of the choroid and AMD biology. Our experiments will lead to a better understanding of this blinding disease and pave the way for treatments that can be utilized for patients with AMD.

 描述（由申请人提供）：我们建议研究年龄相关性黄斑变性（AMD）中脉络膜变性的病理生理学，这是西方世界不可治疗的中央视力丧失的最常见形式。脉络膜是供应外部的复杂血管系统。现在可以使用增强深度成像光学相干断层扫描 (OCT) 在活人体内对视网膜、光感受器和视网膜色素上皮 (RPE) 进行可视化。最近使用 OCT 以及实验室科学家使用供体眼睛对脉络膜进行的研究表明，脉络膜是 AMD 发病机制中的关键组织，特别是因为它与地理萎缩中 RPE 的变性有关（来自。爱荷华州和大型多中心眼科研究）、大量的人类捐赠眼库、组织学、分子生物学、遗传学和图像处理/分析方面的丰富经验，以及最先进的遗传学和分子生物学实验室将为我们提供我们将有一个独特的机会来揭示脉络膜在 AMD 中的关键作用，我们将使用人类捐赠的眼睛来确定 AMD 眼睛中发生的生化途径和解剖学差异，这将使我们能够探索脉络膜损失的解剖细节并确定其发生的原因。 AMD 脉络膜薄弱和眼睛变化的分子基础我们还将探索新型动物模型中脉络膜缺失对视网膜的影响。与 AMD 相关的基因也为使用大量患者群体的脉络膜变性奠定了基础，该项目还有望发现影响脉络膜结构特征和 AMD 生物学的新基因。为可用于 AMD 患者的治疗铺平道路。