586-P: Vitreous and Serum Measurements of Retinol Binding Protein 3 in the Clinical Evaluation of Diabetic Retinopathy

Abstract

The Joslin 50-Year Medalist Study discovered that elevated photoreceptor-secreted Retinol Binding Protein 3 (RBP3) in the retina and vitreous of individuals with extreme duration of type 1 diabetes is associated with long-term protection from advanced diabetic retinopathy (DR), independent of glycemic control. This represents the first neuroretinal protein identified with potential protective activity against the toxic effects of hyperglycemia on the retinal vasculature, a major cause of DR onset and worsening. We extended these findings by correlating vitreous and serum RBP3 concentrations and examining associated clinical characteristics. We developed a novel RBP3 ELISA assay with high sensitivity (0.1-1 nM), specificity (no detection of immunoglobulin G, albumin, or RBP4), and intra-and inter-assay correlations (p<0.001 and p=0.003, respectively). Vascular endothelial growth factor (VEGF) concentrations were measured by ELISA. A total of 101 individuals with type 1 diabetes with mean±SD diabetes duration 44.6±21.0 years, A1c 7.6±1.2%, age 73.5±8.9 years, with 46.5% female, were evaluated. Vitreous RBP3 concentration correlated with vitreous VEGF concentration, age, diabetes duration, cardiovascular disease, and DR severity (p<0.05, all). Mean serum RBP3 concentration was 1000-fold less than vitreous, but correlated with vitreous RBP3 concentration and DR severity (p<0.05, all), even after adjusting for age and A1c. There was a strong association between lower serum RBP3 concentration and increasing age and diabetes duration (p<0.01 and p<0.05, respectively). Vitreous (p=0.01), but not plasma VEGF concentrations were positively associated with DR severity. The fact that serum RBP3 and not plasma VEGF concentrations correlate with DR severity, suggests potential for the systemic measurement of RBP3 in the clinical evaluation of DR and its therapeutic outcomes. Disclosure W. Fickweiler: None. H. Yokomizo: None. K. Park: None. S.M. Paniagua: None. I. Wu: None. D.M. Pober: None. V. Bahnam: None. A. Clermont: Consultant; Self; KalVista Pharmaceuticals, Inc. L.P. Aiello: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Decision Resources Group, KalVista Pharmaceuticals, Inc., Mingsight, Retinal Solutions. Stock/Shareholder; Self; KalVista Pharmaceuticals, Inc. Other Relationship; Self; Optos. J.K. Sun: Research Support; Self; Adaptive Sensory Technology, Boston Micromachines Corporation, Genentech, Inc., KalVista Pharmaceuticals, Inc., Optovue, Incorporated. Other Relationship; Self; Genentech, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. G.L. King: Research Support; Self; Sanofi. Funding National Eye Institute (R01EY026080-01); National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK094333-01); JDRF (17-2013-310); Thomas J. Beatson, Jr. Foundation Inc.; Dianne Nunnally Hoppes Scholarship Fund