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.
Diabetic retinopathy is a major cause of blindness in middle age people with no treatments available that address the underlying causes of this disease due to inability to detect early changes during its development and progression. Here we will develop a novel imaging system that will allow non-invasive monitoring of biochemical and structural changes that occur in retinal vasculature during early stages of diabetes. The results of these studies would advance the NIH mission through better noninvasive detection of early harmful effects of diabetes on retinal vasculature during early stages of diabetes to save vision.
