87-OR: Vitreous Retinol Binding Protein 3 Is Increased in Patients without Advanced Diabetic Retinopathy in Type 1 and Type 2 Diabetes

Retinol Binding Protein 3 (RBP3), a retinol transport protein secreted mainly by photoreceptors, may inhibit progression of diabetic retinopathy (DR) by decreasing glucose uptake and inflammation in the retina. In people with type 1 diabetes with duration of ≥50yrs (Joslin Medalist Study), >40% of Medalists exhibited no to mild non-proliferative diabetic retinopathy (NPDR) and increased expression of RBP3 compared to those with severe DR. We examined 213 vitreous samples from a larger population of Medalists and patients with type 1 and type 2 diabetes with shorter diabetes duration (mean±SD 26.5±12.7 years) from the Joslin Beetham Eye Institute to determine whether vitreous RBP3 levels are correlated with DR severity and progression in a broad population with diabetes. RBP3 was increased in vitreous from people with no diabetes compared to subjects with type 1 and type 2 diabetes (p<0.0001). Type of diabetes (type 1 vs. type 2, p=0.44) and A1c (p=0.68) were not associated with RBP3. In patients with both type 1 and 2 diabetes, vitreous RBP3 levels gradually decreased from the highest concentration in no to mild NPDR (15.7 nM) to the lowest concentrations in advanced DR (moderate-severe: 8.2 nM, p=0.01 vs. no-mild NPDR; active proliferative DR: 8.4 nM, p=0.0003 vs. no-mild NPDR; quiescent proliferative DR: 3.5 nM, p<0.0001 vs. no-mild NPDR). RBP3 was higher in moderate-severe NPDR compared to quiescent PDR (p=0.03). RBP3 concentrations in surgical samples from living donors were lower than those from post-mortem Medalists (p<0.01), but were associated with DR severity in both groups (p=0.03 and p<0.0001, respectively). Increased RBP3 concentrations were associated with reduced risk of PDR development over time (n=34, p<0.001). These findings indicate that elevated vitreous RBP3 is associated with decreased DR severity and decreased risk of PDR development, supporting the postulate that RBP3 is a protective factor and therapeutic target for the progression of DR.