Investigating oxygen metabolism in diabetic retinopathy

项目总结 糖尿病视网膜病变(DR)在美国是导致失明的主要原因，也是两者的主要并发症之一 1型和2型糖尿病。尽管DR被广泛认为是一种由缺血引起的疾病，但目前 DR严重程度的诊断和分级仅基于解剖改变，例如量化 非增殖性疾病的视网膜微血管异常或增殖期的血管生成。作为一名 结果，大多数糖尿病视网膜病变在确诊时是不可逆的，这主要是由于缺乏 量化视网膜缺血和对视网膜潜在机制缺乏了解的技术 缺血症。 这项建议旨在使用一种新的光学相干技术来研究早期糖尿病患者的视网膜缺血 断层扫描技术，它提供了量化视网膜中的氧代谢率(MRO2)的能力 第一次。我们将这项新技术称为可见光光学相干层析成像或VIS-OCT。我们 寻求确定MRO2改变最初发生的时间、MRO2改变的原因以及是否进行干预 在一种独特的1型小鼠模型中，MRO2的表达影响DR的发展。在项目期结束时，我们 将1)建立视网膜MRO2变化的时间线和机制知识 DR的开发和进展以及2)完全优化的VIS-OCT系统，该系统已准备好进行翻译 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.