The retina is one of the most metabolically active tissues in the human body, making it particularly susceptible to hypoxia. In diabetic retinopathy (DR), aberrant oxygen metabolism has been hypothesized to play a pivotal role its pathogenesis. An improved understanding of how imbalances in oxygen delivery and demand lead to the progression of DR is a great but worthwhile challenge, especially considering the rising incidence of diabetes and its position as the leading cause of blindness in the United States. In order to address these questions, the overall objective of the proposed research is to use visible-light optical coherence tomography (vis-OCT) to characterize the oxygen delivery and metabolism in two distinct rodent models of DR. Specifically, we will take advantage of recent developments in OCT to accurately evaluate the inner retinal oxygen delivery (irDO2) and metabolic rate of oxygen (irMRO2) in the db/db mouse and the 50/10 oxygen-induce retinopathy model in rats. The lab has demonstrated that using visible-light illumination, OCT can accurately quantify inner retinal sO2 and blood flow in both mice and rats, which has enabled non-invasive, repeatable measurements of the irDO2 and metabolism irMRO2 in vivo. In the first aim of this proposal, we will use vis-OCT to characterize the longitudinal course to irDO2 and irMRO2 in the db/db mouse. These results will be coupled with investigations of retinal vascular and morphometric changes, which will be made using OCT angiography techniques and retinal thickness measurements, respectively. In the second aim, we will marry the vis-OCT measurements of irDO2 and irMRO2 with histological quantification of retinal thinning, apoptosis, and neovascularization in the rat 50/10 OIR model, a model for the proliferative stage of DR. This is expected to provide a comprehensive overview of the pathogenesis of angiogenesis in this model, which may improve our understanding of the proliferative stages of DR in humans. The insights gained from the results of these two aims will contribute an improved understanding of the metabolic underpinnings of DR and inform future strategies for improved monitoring of the functional status of the retina in DR in humans.
This project aims to better understand how imbalances in retinal oxygen delivery versus oxygen demand lead to the progression of diabetic retinopathy. To this end, we will use a novel imaging technology, visible-light optical coherence tomography, to fully characterize the oxygen delivery and metabolism in two distinct rodent models of diabetic retinopathy.
