Investigating oxygen metabolism in diabetic retinopathy

项目摘要 糖尿病视网膜病变（DR）是美国失明的主要原因，也是两者的主要并发症之一 1型糖尿病的治疗方法尽管DR被广泛认为是缺血驱动的疾病，但目前的研究表明， DR严重程度的诊断和分级仅基于解剖学改变，例如 非增殖性疾病中的异常视网膜微血管或增殖阶段中的血管生成。作为 结果，在大多数DR患者中，诊断时视网膜损伤是不可逆的，主要是由于缺乏 定量视网膜缺血的技术和缺乏视网膜缺血的潜在机制的知识， 缺血 这项建议的目的是调查视网膜缺血在早期糖尿病使用一种新的光学相干 断层扫描技术，它提供了量化视网膜中氧代谢率（MRO 2）的能力， 第一次我们将这种新技术称为可见光光学相干断层扫描或vis-OCT。 寻求确定MRO 2改变最初发生的时间，MRO 2改变的原因，以及是否干预 MRO 2的表达影响了独特的1型小鼠模型中DR的发展。在项目结束时，我们 将1）建立视网膜MRO 2变化的时间线和机制知识， DR的发展和进步; 2）完全优化了准备平移的vis-OCT系统 进行下一阶段的病人测试

PROJECT SUMMARY Diabetic retinopathy (DR) is a leading cause of blindness in the US and one of the major complications of both Type 1 and Type 2 diabetes. Although DR is widely accepted to be an ischemia-driven disease, the current diagnosis and grading of DR severity is based solely on anatomic alterations such as the quantification of abnormal retinal microvasculature in non-proliferative disease or angiogenesis in proliferative stages. As a result, retinal impairment is irreversible in most DR patients when diagnosed, largely due to the lack of technology to quantify retinal ischemia and the lack of knowledge of the underlying mechanism of retinal ischemia. This proposal aims to investigate retinal ischemia in early diabetes using a novel optical coherence tomography technology, which offers the capability to quantify metabolic rate of oxygen (MRO2) in the retina for the first time. We refer to this new technology as visible-light optical coherence tomography or vis-OCT. We seek to identify when MRO2 alterations initially occur, the causes of MRO2 alterations, and whether intervention of MRO2 affects the development of DR in a unique Type 1 mouse model. At the end of the project period, we will have 1) established a time line and mechanistic knowledge of retinal MRO2 changes during the development and progression of DR and 2) fully-optimized the vis-OCT system that is ready to be translated for the next-stage patient testing.