The Joslin Medalist Study, which characterizes people with type 1 diabetes duration of 50 years or more, reported that the levels of Retinol Binding Protein 3 (RBP3) are increased in the retina and vitreous of Medalists who are protected from the development of severe diabetic retinopathy (DR). This protective capacity of RBP3 is potentially mediated by its ability to delay the uptake of glucose into the cells of the retinal vasculature and neural retina in hyperglycemia. This study correlated the relationship between DR severity and neural retinal layer thickness with vitreous and serum RBP3 levels in a broad population of people with diabetes. Optical coherence tomography (OCT) was performed to obtain neural retinal layer thicknesses and structure. Specific ELISA assays were developed to measure vitreous and serum RBP3 concentrations in individuals with type 1 and type 2 diabetes recruited from the Joslin Beetham Eye Institute, Medalist Study, and the FinnDiane study. Vitreous RBP3 concentration was associated with DR severity (p<0.05), diabetes duration (p=0.02), age (p=0.01), and HDL (p<0.05) in the Medalists (n=68), individuals with shorter duration of type 1 and type 2 diabetes (mean±SD 28±14 years, n=24), and nondiabetic controls (n=20). OCT showed that thinning of the inner nuclear layer, outer nuclear layer, and the photoreceptor layer was associated with decreased vitreous RBP3 concentration (all p<0.0001). Serum RBP3 concentrations were more than 1000-fold less than those in vitreous, but correlated positively with vitreous RBP3 concentration (p<0.05). The presence of laser photocoagulation was associated with decreased serum RBP3 concentration (p=0.005). Repeated testing at 5 years showed that baseline and 5 year RBP3 serum concentrations were correlated in the Medalist Study (r=0.64, p=0.003) and the FinnDiane Study (r=0.77). These findings suggest that measurement of RBP3 systemically may be potentially useful in the clinical screening of DR.
W. Fickweiler: None. K. Park: None. E. Wolfson: None. H. Park: None. H. Yokomizo: None. I. Wu: None. D. Gordin: Consultant; Self; GE Healthcare. Speaker’s Bureau; Self; AstraZeneca, Fresenius Medical Care, Novo Nordisk A/S. Other Relationship; Self; CVRx, Sanofi-Aventis. V. Harjutsalo: None. P. Groop: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi, Sanofi. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medscape, Merck Sharp & Dohme Corp., Mundipharma International. L.P. Aiello: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; KalVista Pharmaceuticals, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; KalVista Pharmaceuticals, Inc. Other Relationship; Self; Optos. J. Sun: Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Novo Nordisk Inc., Optovue, Inc., Roche Pharma. Other Relationship; Self; Merck Foundation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Roche Pharma. G.L. King: Research Support; Self; Janssen Pharmaceuticals, Inc.
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; Dianne Nunnally Hoppes Scholarship Fund