Implementing a novel multimode 3D retinal imaging system to investigate metabolism and vascular disruptions in diabetic retinopathy

糖尿病引起视网膜微血管和细胞氧化还原并发症和糖尿病性视网膜病变的发展 视网膜病变（DR）。糖尿病对视网膜神经血管功能产生不利影响的早期机制， 完整性和糖尿病视网膜病变进展的认识很少。这种缺乏了解的情况阻碍了 无法早期和非侵入性地检测和研究这些变化。有一个至关重要的需要， 非侵入性成像工具和定量生物标志物作为糖尿病对视网膜的不良影响的指标 神经血管、代谢和功能。本研究的主要前提是解决 现有的工具，同时和非侵入性地测量线粒体氧化还原状态，和视网膜神经血管 糖尿病期间的诚信这些测量将提供生物标志物，可用于初级保健 设置. 这个AREA项目的主要假设是糖尿病刺激线粒体功能障碍， 增加的OxS和视网膜中的神经血管破坏，这可以非侵入性地检测到。我们的团队将 实施MM-cSLO以评估糖尿病秋田/+小鼠中这些变化， 线粒体氧化还原状态和神经血管完整性在视网膜功能障碍中是关键的。有三个具体的 设计并实现了一种多模式共焦扫描激光检眼镜 （MM-cSLO）用于DR生物标志物的高分辨率时空成像。2)确定视网膜的变化 糖尿病期间的血管网络、氧合和线粒体功能障碍。 这些研究的结果将确定线粒体功能障碍和神经血管损伤的过程。 糖尿病早期诊断的中断改变。使用这种非侵入性成像方式可以允许 基于个体化风险与获益评估的糖尿病患者的检测和治疗， 真实的时间。视网膜成像的解剖和功能信息的相关性有助于阐明 视网膜成像结果的功能后果，并为它们作为结果的使用提供进一步的支持 治疗干预措施。如果这些检测和治疗方法被证明是有效的， 立即在转化研究中进行评估。 这一领域的应用将导致一个独特的跨学科的教育平台，培训UWM 本科生和研究生。有一个非常广泛和非常丰富的教育机会，为学生 学习电子学、光学、仪器、生物学、生物化学、计算机编程， 只有在这种跨学科方法中才能完成的具体研究项目。这样的 教育平台将增加UWM电气专业本科生的参与 工程和生物医学工程的研究。这些研究活动的成功实施将 促进从实验室到临床床旁的长期、可持续的目标。

Diabetes causes microvascular and cellular redox complications in the retina and development of diabetic retinopathy (DR). The early mechanisms by which diabetes adversely affects retinal neurovascular function and integrity, and diabetic retinopathy progression, are poorly understood. This lack of understanding is hampered by the inability to detect and study these changes early and non-invasively. There is a crucial need for noninvasive imaging tools and quantitative biomarkers as indicators of diabetes’ adverse effect on the retinal neurovasculature, metabolism, and function. The main premise of this study is addressing the significant gap in existing tools to simultaneously and noninvasively measure mitochondrial redox state, and retinal neurovascular integrity during diabetes. These measurements will provide biomarkers, which could be used in primary care settings. The main hypothesis of this AREA project is that diabetes stimulates mitochondrial dysfunction, increased OxS, and neurovascular disruption in the retina that can be detected non-invasively. Our team will implement a MM- cSLO to evaluate these changes in diabetic Akita/+ mice to test that early disruption of mitochondrial redox states and neurovascular integrity is critical in retinal dysfunction. There are three specific aims to test these hypotheses.1) Design and implement a multimodal confocal scanning laser ophthalmoscope (MM-cSLO) for high resolution spatiotemporal imaging of DR biomarkers. 2) Determine changes in the retinal vascular network, oxygenation, and mitochondrial dysfunction during diabetes. The outcome of these studies will establish the course of mitochondrial dysfunction and neurovascular disruption in early diagnosis of diabetes changes. The use of this non-invasive imaging modality could permit detection and treatment of patients with diabetes based upon individualized risk versus benefit assessments in real time. Correlation of anatomical and functional information from retinal imaging could help elucidate the functional consequences of the findings of retinal imaging and provide further support for their use as outcomes measures of therapeutic intervention. If these detection and treatment methods are proven effective, they could be immediately evaluated in translational research. This AREA application will lead to a unique interdisciplinary educational platform for training UWM undergraduate and graduate students. There is a very broad and very rich educational opportunity for students to learn about electronics, optics, instrumentation, biology, biochemistry, computer programing wrapped in specific research project that can only be accomplished in such an interdisciplinary approach. Such an educational platform would increase the participation of UWM’s undergraduates majoring in electrical engineering and biomedical engineering in research. Successful implementation of these research activities will facilitate the long term, sustainable goal of translation from bench side to clinical bedside.