MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY

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DESCRIPTION (provided by applicant): Proliferative retinopathy is a leading cause of blindness in adults and children. It is manifested as hypoxia induced malignant angiogenesis at retinal surface that will deteriorate vision and lead to retinal detachment to cause permanent vision loss. Medical therapy for proliferative retinopathy is non-effective. Surgical medical treatment to ablate peripheral retina is the method to prevent the disease progression at the cost of losing peripheral vision. This treatment has prominent side effects on the visual system and may not stop the disease progression in some patients. Current interests on developing more effective therapy for proliferative retinopathy are: to develop anti-angiogenesis drug that specifically inhibit retinal neovascularization; to explore predictive markers of the diseases for preventive therapy. We have developed high resolution magnetic resonance imaging (MRI) technique that specifies multiple retinal layers with layer specific T1, T2, and apparent diffusion coefficient (ADC) in rodents. Our preliminary studies have demonstrated that MRI is sensitive to cell injury after retinal ischemia or photoreceptor degeneration. We have also shown that 1v23-integrin targeted nanoparticles specifically bind to corneal neovasculature and provide localized MRI contrast in rabbits. Based on our preliminary result, we hypothesize that hypoxia induced retinal angiogenesis could be specifically delineated with molecular MRI using 1v23-integrin targeted nanoparticles. Hypoxia will also cause retinal cell injury that will result in changes in ADC before retinal angiogenesis. To test our hypothesis, a rat model of hypoxia induced retinal neovascularization is selected. We predict that 1v23-integrin targeted nanoparticles will specifically bind to retinal neovasculature for molecular MRI of retinal angiogenesis. We also expect changes in ADC in hypoxia injured retinal cells can be detected early with diffusion weighted magnetic resonance imaging. The proposed study, if successful, will provide novel MRI biomarkers for early diagnosis of retinal neovascularization that feature cell hypoxia and angiogenesis. PUBLIC HEALTH RELEVANCE: Retinal angiogenesis is the leading cause of blindness in premature infants and diabetic adults. The proposed research aims to develop techniques for early diagnosis of retinal angiogenesis using nanoparticles and non-invasive medical imaging method.