This Small Business Innovation Research project aims to develop an innovative eye drop formulation for the treatment of diabetic retinopathy. The goal of this proposal is to develop substantial efficacy, safety, and pharmacokinetic data to support the clinical development of topical fenofibrate. We hypothesize that topical application of fenofibrate can reduce vision loss and neovascularization in animal models of diabetes and retinal disease. The goal of this proposal is to 1) evaluate the efficacy of topical fenofibrate on preventing visual acuity loss in a rat model of streptozotocin-induced diabetes We will give fenofibrate eye drops either two or four times a day for 16 weeks. We will measure the change of visual acuity over this time period. The long term goal (Phase 2) is to perform safety studies and find a commercial manufacturer for the formulation.
Public Health Relevance Statement: Public Health Relevance: Nearly all patients with type 1 diabetes, and >60% of type 2 diabetic patients will develop some form of retinopathy and visual loss in their lifetime. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPAR?) agonist that has been shown in both The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trials to reduce the progression of diabetic retinopathy in diabetic patients. Oral fenofibrate appears to have limited systemic benefit in diabetic patients, thus the topical application of fenofibrate for diabetic eye disease represents a more targeted and safe approach to treat diabetic retinopathy.
Project Terms: Affect; Age; Agonist; angiogenesis; Animal Model; aqueous; Attenuated; Back; base; Blindness; Blood capillaries; Blood Vessels; capillary; Cardiovascular Diseases; cardiovascular disorder prevention; cardiovascular risk factor; Cell Death; Choroid; Clinical; Clinical Research; Clinical Trials; Complications of Diabetes Mellitus; Contrast Sensitivity; Cream; cytokine; Data; Development; Diabetes Mellitus; diabetic; diabetic patient; diabetic rat; Diabetic Retinopathy; DNA Nucleotidylexotransferase; Drug Delivery Systems; Drug Kinetics; Effectiveness; Electroretinography; Emulsions; endothelial dysfunction; Enrollment; Enzyme-Linked Immunosorbent Assay; Event; Extravasation; Eye; Eye diseases; Eyedrops; FDA approved; Fenofibrate; fenofibric acid; Formulation; Frequencies; Generations; Glial Fibrillary Acidic Protein; Goals; high throughput screening; Hyperemia; hypoxia inducible factor 1; Ice; Impairment; Inflammation; Inflammatory; innovation; Insulin-Dependent Diabetes Mellitus; Intercellular adhesion molecule 1; Intervention; Kidney; Kidney Failure; Label; Legal patent; Leukostasis; Libraries; lipoprotein triglyceride; Manufacturer Name; Measures; Mediator of activation protein; meetings; Microvascular Dysfunction; Modeling; Monocyte Chemoattractant Protein-1; Mus; neovascularization; Nerve; Nerve Degeneration; novel; Nuclear; Oils; Oral; Oral Administration; Organ; overexpression; Oxygen; Patients; Pharmaceutical Preparations; Phase; PPAR alpha; Preparation; prevent; protective effect; public health relevance; Rattus; Reactive Oxygen Species; research clinical testing; Research Project Grants; Retina; Retinal; Retinal Diseases; Retinal Neovascularization; retinal neuron; Safety; safety study; Schedule; Severities; Small Business Innovation Research Grant; small molecule; Solvents; Streptozocin; Stress; Structure of retinal pigment epithelium; surfactant; synthetic polymer Bioplex; Time; Tissues; Topical application; Trypsin; Vascular Endothelial Growth Factors; Visual Acuity; Visual impairment
