Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy

PURPOSE: Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF(165)a) and antiangiogenic (VEGF(165)b) VEGF isoforms and its soluble receptors for severity of DR. METHODS: The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF(165)a (proangiogenic), VEGF(165)b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF(165)a and a decrease in the level of VEGF(165)b, was observed with the severity of the disease. Increased differences between VEGF(165)a and VEGF(165)b i.e. VEGF(165)a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001). CONCLUSIONS: The increased difference or imbalance between the pro- (VEGF(165)a) and antiangiogenic (VEGF(165)b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform.