Choroidal Disease Mechanisms in AMD

AMD 的脉络膜疾病机制

基本信息

批准号：
9903326
负责人：
Elliott H Sohn
金额：
$ 38.13万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9903326
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&apos s basal membrane structure Candidate Disease Gene Cathepsins Cellularity Choroid Choroid Diseases Collection Complex Data Disease Dropout Eye Fibrosis Functional disorder Genes Genetic Histologic Histology Human Image Iowa Laboratories Laboratory Scientists Medical Metalloproteases Modality Molecular Molecular Biology Molecular Genetics Morphology Nonexudative age-related macular degeneration Optical Coherence Tomography Pathogenesis Pathway interactions Patients Phenotype Photoreceptors Play Research Research Personnel Retina Retinal Degeneration Retinal Photoreceptors Role Structure Structure of retinal pigment epithelium Testing Thick Thinness Tissues Vascular System Vascular blood supply Vision Western World cohort disorder of macula of retina experience experimental study genomic locus geographic atrophy image processing in vivo insight macula multidisciplinary next generation next generation sequencing normal aging novel novel therapeutics optical imaging programs public health relevance tool translational study

项目摘要

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（由适用提供）：我们建议研究与年龄相关的黄斑变性（AMD）中脉络膜变性的病理生理学，这是西方世界中最常见的中央视力损失的最常见形式。现在，可以使用增强的深度成像光学相干断层扫描（OCT）将脉络膜，即供应外视网膜，光感受器和视网膜色素上皮（RPE）的复杂血管系统（RPE）。临床医生使用OCT对脉络膜的最新研究以及实验室科学家使用供体眼睛的研究表明，脉络膜是发病机理AMD中的关键组织，尤其是与地理萎缩中RPE的变性有关。访问AMD的患者（来自爱荷华州和大型多中心眼研究），大型人类供体的收集，在组织学，分子生物学，遗传学和图像处理/分析以及最先进的遗传学和分子生物学实验室方面的丰富经验，将为我们提供独特的机会，以使我们能够在AMD中揭示纯脊体的重要作用。我们将使用人类的供体眼来确定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学细节，并确定薄脉络膜和眼睛用AMD变化的分子基础。我们还将探索新型动物模型中脉络膜损失对视网膜的后果。最后，我们将利用我们在遗传学方面的丰富经验来评估已经与AMD有关的基因的程度也构成了使用非常大的患者队列的脉络膜变性的基础。该项目还具有发现影响脉络膜和AMD生物学结构特征的新基因。我们的实验将使人们更好地了解这种盲目疾病，并为可以用于AMD患者使用的治疗铺平道路。