Diabetic Retinopathy: Genetics and Neurodegeneration (MSN246458)

项目摘要/摘要 糖尿病(DM)是导致工作年龄的成年人视力丧失的主要原因。它的流行率是 尽管在知识和治疗方面取得了长足的进步，但我们对导致 糖尿病患者的视力损失仍然有限。高血糖和糖尿病病程有助于但不能完全解释 易患糖尿病视网膜疾病。鉴于糖尿病视网膜疾病的易感性 在家庭中聚集，遗传风险因素被认为是重要的，但到目前为止还没有确定的因素 牵连其中。此外，来自小型研究的数据表明，糖尿病视网膜有更多的表型 这种疾病比目前在临床实践中认识到的更多。糖尿病视网膜疾病传统上是 主要被认为是一个血管过程：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。随着成像方式和图像分析算法的改进， 对糖尿病视网膜疾病的一种新的临床表现--糖尿病视网膜的认识日益增加 神经变性(DRN)。这表现为视网膜神经纤维(RNFL)厚度和/或 光学相干断层扫描(OCT)图像上的神经节细胞层(GCL)。到目前为止，人们对DRN知之甚少， 而且它在糖尿病患者临床治疗中的作用还没有确定。然而，如果视网膜 神经退行性变会发生并且是进行性的，它会导致糖尿病患者的严重视力困难。 DRN可能解释了糖尿病视网膜患者以前无法解释的视力不良结果 疾病，尽管有标准的护理和治疗。Channa博士是一位视网膜专家，以前的研究经验是 DME新治疗方法的视网膜成像和临床试验。在这个K23职业发展奖中，她 建议使用具有全国代表性的数据集，英国生物库队列来：1)提高我们对 通过OCT成像测定糖尿病患者(无糖尿病患者)的RNFL和GCL厚度的DRN 或DME)与那些没有DM的人进行比较2)确定与DR、DME和 DRN.Channa博士提出了一项职业发展计划，其中包括指导、课程作业、出版 和临床时间。这将使她成为一名独立的临床医生兼科学家，拥有翻译方面的专业知识 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术来阐明 糖尿病患者视力丧失的途径，最终导致新疗法的发展。她 研究工作和职业发展将在大学的学术和合作环境中进行 世界上最大的医疗中心，在那里她有机构支持和指导来发展成为一名 独立的临床医生兼科学家。

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.