Elevated Retinol Binding Protein 3 Concentrations Are Associated with Decreased Vitreous Inflammatory Cytokines, VEGF, and Progression of Diabetic Retinopathy

OBJECTIVE: To correlate inflammatory cytokines and vascular endothelial growth factor (VEGF) in vitreous and plasma with vitreous Retinol Binding Protein 3 (RBP3), diabetic retinopathy (DR) severity, and DR worsening in population with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: RBP3, VEGF and inflammatory cytokines were measured in plasma and vitreous samples (n=205) from subjects of the Joslin Medalist Study and Beetham Eye Institute. RESULTS: Higher vitreous RBP3 concentrations were associated with less severe DR (p<0.0001), and reduced risk of developing proliferative DR (PDR, p<0.0001). Higher RBP3 correlated with increased photoreceptor segment thickness and lower vitreous IL-12, TNF-a and TNF-b (p<0.05). PDR was associated with lower vitreous IFN-γ and IL-10, and higher VEGF, IL-6, and IL-15 (p<0.05), but was not associated with their plasma concentrations. CONCLUSIONS: Higher vitreous RBP3 concentrations are associated with less severe DR and slower rates of progression to PDR, supporting its potential as a biomarker and therapeutic agent for preventing DR worsening, possibly by lowering retinal VEGF and inflammatory cytokines.