42-OR: Association of Vitreous Retinol Binding Protein 3 with Inflammatory Cytokines and Progression of Diabetic Retinopathy in Type 1 and Type 2 Diabetes
Authors: FICKWEILER WARD , PARK HYUNSEOK , PARK KYOUNGMIN , MITZNER MARGALIT G. , ROBINSON DEVON B. , CHOKSHI TANVI , BOUMENNA TAHANI , GAUTHIER JOHN , WU I-HSIEN , CAVALLERANO JERRY D. , AIELLO LLOYD P. , SUN JENNIFER , KING GEORGE L. 
Published: May 2022

Although inflammatory cytokines and vascular endothelial growth factor (VEGF) have been proposed to underlie the progression of diabetic retinopathy (DR) , there remains an important need to identify biomarkers for early stages of DR. Findings from the Joslin Medalist Study, composed of individuals who have had insulin-dependent diabetes for 50 years or longer, showed that Retinol Binding Protein 3 (RBP3) was significantly higher both in retina and vitreous samples with no to mild DR compared to those with proliferative DR (PDR) . In this study, we examined vitreous and plasma samples from 2people with type 1 and type 2 diabetes from the Joslin Beetham Eye Institute and Medalist Study to evaluate the relationship between vitreous RBP3, inflammatory cytokines, and DR severity and progression. PDR was associated with lower levels of IL- (P=0.007) , IFN-γ (P=0.001) , and higher levels of IL-15 (P=0.01) and IL-6 (P=0.02) in vitreous. Vitreous VEGF was positively associated with increasing DR severity in surgical samples (P&lt;0.05) . Plasma VEGF was not associated with vitreous VEGF concentration. No significant relationships were found between inflammatory markers in the vitreous and plasma from the same individual. Increased vitreous RBP3 concentration was associated with less severe DR in all eyes (P&lt;0.0001) , post-mortem (P&lt;0.0001) and surgical samples from type 1 and type 2 diabetic patients (P=0.03) with diabetes duration of &lt;50 years (mean±SD 27±13 years) . Higher vitreous RBP3 concentration was associated with lower risk of PDR onset (P&lt;0.0001) . Lower vitreous TNF-α, TNF-β, and VEGF were associated with increased vitreous RBP3 concentration (P&lt;0.05, all) . These findings suggest that inflammatory cytokines and risk of DR worsening may be decreased by RBP3, supporting its potential use as biomarker for severity and progression of DR.

Disclosure
W.Fickweiler: None. J.D.Cavallerano: None. L.P.Aiello: Consultant; KalVista Pharmaceuticals, Inc., Novo Nordisk, Stock/Shareholder; KalVista Pharmaceuticals, Inc. J.Sun: Consultant; American Diabetes Association, American Medical Association, Research Support; Adaptive Sensory Technology, Boehringer Ingelheim International GmbH, Genentech, Inc., Jaeb Center for Health Research, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Optovue, Incorporated, Physical Sciences, Inc, Roche Pharmaceuticals. G.L.King: Advisory Panel; Medtronic, Research Support; Janssen Pharmaceuticals, Inc. H.Park: None. K.Park: None. M.G.Mitzner: None. D.B.Robinson: None. T.Chokshi: None. T.Boumenna: None. J.Gauthier: None. I.Wu: None.

Funding
American Diabetes Association (7-21-PDF-022) ; National Eye Institute (R01EYE26080-01) , the National Institute of Diabetes and Digestive and Kidney Diseases and National Institutes of Health (DP3-DK-094333-01) ; JDRF (17-2013-310) ; the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund