Diabetic Retinopathy: Genetics and Neurodegeneration (MSN246458)

糖尿病视网膜病变：遗传学和神经变性 (MSN246458)

基本信息

批准号：
10474525
负责人：
Roomasa Channa
金额：
$ 24.88万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10474525
关键词：
Address Adult Affect Algorithmic Analysis American Appearance Artificial Intelligence Bioinformatics Blindness Blood Vessels Clinical Clinical Management Clinical Research Clinical Trials Computational algorithm Data Data Analyses Data Set Development Development Plans Diabetes Mellitus Diabetic Retinopathy Disease Disease Pathway Environment Family Fundus Future Ganglion Cell Layer Genes Genetic Genetic Predisposition to Disease Genomics Goals Hyperglycemia Image Image Analysis Intervention K-Series Research Career Programs Knowledge Lead Measurement Medical center Mentors Mentorship Methods Molecular Nerve Degeneration Nerve Fibers Optical Coherence Tomography Outcome Participant Pathway interactions Patients Persons Phenotype Predisposition Prevalence Prevention Process Publications Race Regression Analysis Reporting Research Retina Retinal Diseases Retinal Ganglion Cells Risk Factors Role Sample Size Scanning Scientist Specialist Techniques Testing Thick Time Training Translating Translational Research Vascular Endothelial Growth Factors Vision Visual Work aged base biobank career development clinical practice cohort collaborative environment diabetes management diabetic disability experience family genetics fiber cell genetic risk factor genome wide association study genomic data illness length imaging modality improved large datasets macular edema nerve damage novel novel therapeutics population based prevent retinal imaging screening skills standard of care

项目摘要

PROJECT SUMMARY/ABSTRACT Diabetes mellitus (DM) is the leading cause of vision loss among working aged adults. Its prevalence is increasing and despite the strides in knowledge and treatments, our understanding of the pathways leading to vision loss in DM remains limited. Hyperglycemia and duration of DM contribute to but do not fully explain the predisposition to develop diabetic retinal diseases. Given the predisposition for diabetic retinal diseases to cluster in families, genetic risk factors are thought to be important but none has so far been definitively implicated. Furthermore, data from small studies suggest that there are more phenotypes of diabetic retinal disease than are currently recognized in clinical practice. Diabetic retinal disease has traditionally been considered primarily a vascular process: diabetic retinopathy (DR) and diabetic macular edema (DME) are the main clinical manifestations. With improved imaging modalities and image analysis algorithms, there has been increasing recognition of a new clinical manifestation of diabetic retinal disease, diabetic retinal neurodegeneration (DRN). This is visible as alterations in thickness of retinal nerve fiber (RNFL) and/or ganglion cell layer (GCL) on optical coherence tomography (OCT) images. To date, DRN is poorly understood, and its role in clinical management of patients with DM has not been established. However, if retinal neurodegeneration occurs and is progressive, it can lead to profound visual difficulties for patients with DM. DRN may account for previously unexplained poor visual outcomes among patients with diabetic retinal disease despite standard of care treatment. Dr. Channa is a retina specialist, with prior research experience in retinal imaging and clinical trials of novel treatments for DME. In this K23 career development award she proposes to use a nationally representative dataset, the UK Biobank cohort to: 1) improve our understanding of DRN by determining RNFL and GCL thickness, using OCT imaging, in participants with DM (who have no DR or DME) compared to those who do not have DM 2) determine genetic factors associated with DR, DME and DRN. Dr. Channa proposes a career development plan, which includes mentorship, coursework, publications and clinical time. This will situate her as an independent clinician-scientist with expertise in translational research employing bioinformatics and computational skills in genomics and retinal image analysis to elucidate pathways of vision loss among patients with DM, ultimately leading to development of novel therapies. Her research work and career development will take place in the academic and collaborative environment of the largest medical center in the world, where she has institutional support and mentorship to develop as an independent clinician-scientist.

项目概要/摘要糖尿病（DM）是导致工作老年人视力丧失的主要原因。其患病率是尽管知识和治疗方法取得了长足的进步，但我们对导致疾病的途径的理解仍在不断增加 DM 患者的视力丧失仍然有限。高血糖和糖尿病持续时间有助于但不能完全解释患糖尿病视网膜疾病的倾向。鉴于糖尿病视网膜疾病的易感性家庭聚集，遗传风险因素被认为很重要，但迄今为止还没有明确的结论受牵连。此外，小型研究的数据表明糖尿病视网膜有更多的表型疾病比目前临床实践中认识的疾病要多。糖尿病视网膜疾病传统上被认为是主要被认为是血管过程：糖尿病视网膜病变（DR）和糖尿病黄斑水肿（DME）是主要临床表现。随着成像模式和图像分析算法的改进，人们越来越认识到糖尿病视网膜疾病的新临床表现——糖尿病视网膜神经退行性变（DRN）。这可以通过视网膜神经纤维 (RNFL) 厚度的变化和/或光学相干断层扫描 (OCT) 图像上的神经节细胞层 (GCL)。迄今为止，人们对 DRN 的了解还很少，其在 DM 患者临床管理中的作用尚未确定。然而，如果视网膜神经退行性疾病会发生并且是进行性的，它可能导致 DM 患者出现严重的视力困难。 DRN 可能是糖尿病视网膜患者先前无法解释的视力不良的原因尽管进行了标准护理治疗，仍患有疾病。 Channa 博士是一位视网膜专家，拥有以下方面的研究经验： DME 新疗法的视网膜成像和临床试验。在这次K23职业发展奖中她建议使用具有全国代表性的数据集，即英国生物银行队列来：1）提高我们对 DRN 通过使用 OCT 成像确定 DM 参与者（没有 DR）的 RNFL 和 GCL 厚度或 DME）与那些没有 DM 的人相比 2）确定与 DR、DME 和 DRN。 Channa 博士提出职业发展计划，其中包括指导、课程作业、出版物和临床时间。这将使她成为一名独立的临床医生科学家，拥有转化方面的专业知识利用基因组学和视网膜图像分析中的生物信息学和计算技能来阐明糖尿病患者视力丧失的途径，最终导致新疗法的开发。她研究工作和职业发展将在该中心的学术和协作环境中进行世界上最大的医疗中心，在那里她获得了机构支持和指导，以发展成为一名独立的临床医生科学家。