Diabetic retinopathy (DR), a complication of diabetes and the leading cause of blindness in working-age adults, is a retinal disease whose prolonged course typically begins years prior to diagnosis. DR is presently diagnosed by clinical findings on examination;by the time these are visible, significant irreversible damage to the retina has already occurred for most patients. Insufficient oxygen delivery and hypoxia associated with the energy-demanding photoreceptors has been implicated in the early stage of the disease. Such oxygen delivery-utilization mismatch ultimately precipitates late stage neovascularization and vision loss. We hypothesize that the mismatch in oxygen delivery-utilization in the retina results in abnormal blood flow and tissue oxygenation in the early stage of DR before vision loss. Currently, there are no existing non- invasive imaging technologies available to detect these early changes, when intervention could be most effective. Imaging technologies that can detect early changes in blood flow and oxygenation could accelerate early detection of DR, offer focused screening of population at risk, and enable longitudinal treatment monitoring. Early detection has the potential to prevent blindness and improve treatment outcomes, including quality of life. Most existing retinal imaging techniques lack depth-resolved information (except optical coherence tomography for anatomical imaging) and rely on optical transparency which is frequently hampered by media opacity (e.g., cataracts and vitreous hemorrhages). In contrast, MRI can provide anatomical, physiological, and functional data with lamina-specific depth resolution. Its application to the thin retina, however, has been challenging. Our group pioneered multi-parametric, layer-specific retinal MRI in animals and has demonstrated some unique advantages. This proposal aims to take the first step to translate this innovative approach to study the human retina. Our central hypothesis is that: i) high-resolution MRI can provide anatomical, physiological, and functional images of the human retina with laminar resolution, and ii) functional and physiological changes in DR patients will occur before structural abnormalities can be detected.
This proposal outlines: 1) the development of MRI approaches to resolve structural, physiological and functional laminar specificity of the human retina at very high spatial resolution, and 2) application to investigate a selected group of human diabetic retinopathy patients to demonstrate feasibility. This project has strong clinical significance and potential impact to the field in that it can provide 1) an early marker of diabeti retinopathy and for monitoring therapeutic intervention and 2) powerful insights into how retinal and choroidal blood flow and oxygenation are regulated and how diabetic retinopathy affects the two vasculatures and the neural tissues they subserve. Data from these animal studies should advance these areas of research, open up new avenues for retinal research, and lay the foundation for future human studies.