Non-Invasive Molecular Imaging in Early Diagnosis of Diabetic Complications
Diabetic retinopathy (DR), a microvascular manifestation of diabetes, is a leading cause of adult vision loss. Early detection and treatment can prevent vision loss from DR. However, there is currently no way to detect early molecular or cellular changes in human diabetic patients. Existing methods of clinical examination only detect the structural damages. Therefore, treatment usually occurs too late to prevent significant vision deterioration. It would be of tremendous benefit to the patients, if DR could be diagnosed before the manifestation of clinical signs of the disease and the occurrence of irreversible structural damages. Our goal is to develop and establish a non-invasive molecular imaging technique that in human patients quantitatively depicts earliest signs of diabetic micro-vasculopathy. Our approach is inspired by how the organism’s own immune cells detect slightest signs of disease, for instance during their recruitment to sites of inflammation. We generate custom-designed imaging probes that bind to specific endothelial markers. Since the eye provides a unique portal for light-based imaging, the binding interaction of these agents to retinal microvasculature can be visualized and will give precise and quantitative knowledge about the status of the retinal health. This new approach extends the in vivo detection capabilities to the cellular and molecular level, which amounts to a categorical advancement in imaging. Our imaging probes provide a distinct type of signal compared to other molecular imaging approaches, revealing expression and site density of the molecules to be imaged in vivo. Our aims are to 1) establish our molecular imaging for early diagnosis of diabetic changes in the retina and use it for mechanistic studies and identification of new biomarkers of diabetic retinopathy. Here we investigate adhesion molecules and growth factor receptors as candidate marker for evaluation of DR, and 2) use molecular imaging in the retina to gain insights about other diabetic complications that are not as easily accessible, such as atherosclerosis, kidney or liver changes. Completion of this research will result in powerful and versatile tools that enable basic researchers and clinicians to in-depth understanding of the dynamic molecular and cellular changes that occur in diabetic microvasculopathy, identify and characterize new molecular markers and test efficacy of new therapeutics.

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