Dietary Control of Angiogenesis in Retinopathy Model: Basis for Clinical Trials

Our overall goal is to understand the mechanism of ROP and diabetic retinopathy and to find therapies to treat both phases of the disease. The proposed experimental plan is designed to identify a new nutritional and pharmacologic intervention to prevent diabetic and other retinopathy (DR), to determine complex mechanisms of action with a quantitative comparative transcriptional profiling technique and to develop new surrogate markers for DR. This blinding disease is characterized by inflammatory components with late neovascularization. Lipid based molecules act as effectors of inflammation and angiogenesis; particularly potent are certain eicosanoids, derived from the 20 carbon long chain polyunsaturated fatty acids (LCPUFAs), via cyclooxygenase (COX) and lipoxygenase (LOX) pathways. COX and LOX are inducible and constitutively expressed in retina. Opposing anti-inflammatory and anti-angiogenic influence is found with intake of omega 3 ?LCPUFAs. As LCPUFA tissue status is modified by and dependent on dietary intake, these nutrients are reasonable choices for interventions to prevent DR with foods that are not usually consumed in the Western diet. Inhibition of COX-2 decreases inflammation and inhibits angiogenesis. It may be synergistic with ?-3 LCPUFA intake.