Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy

Abstract

AimsTo determine the associations between the levels of certain cytokines in the aqueous humor and the severity of diabetic retinopathy. MethodsA total of 103 patients (one eye per patient) who received intravitreal injection with ranibizumab for diabetic retinopathy were enrolled and divided into 3 groups: nonproliferative diabetic retinopathy (NPDR) with macular edema group (42 eyes), proliferative diabetic retinopathy (PDR) group (40 eyes) and neovascular glaucoma due to PDR (NVG-PDR) group (21 eyes). The concentrations of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor were measured. ResultsIn this study, 42, 40 and 21 patients (one eye per patient) were included in the NPDR, PDR and NVG-PDR groups, respectively. The median concentrations of IL-6, IL-8, IL-10, VEGF, TGF-β, VCAM-1, ICAM-1 and MCP-1 in the groups were measured. The levels of these 8 cytokines increased with the severity of diabetic retinopathy, especially in the NVG-PDR group. Compared with those in the NPDR group, the aqueous concentrations of these 8 cytokines were higher in the PDR group and were the highest in the NVG-PDR group. There were significant differences in all cytokines among the three groups (P < 0.05). Multivariate analysis showed that in the NPDR and PDR groups, the risk of PDR associated with elevated levels of TGF-β (P = 0.0004, OR 1.11, 95% CI [1.05–1.18]) and ICAM-1 (P = 0.0408, OR 10.75, 95% CI [1.10–104.61]). In the PDR and NVG groups, the risk of NVG associated with elevated levels of IL-10 (P = 0.0486, OR 0.7040, 95% CI [0.4966, 0.9979]), VEGF (P = 0.0279, OR 0.9963, 95% CI [0.9931, 0.9996]), and VCAM-1 (P = 0.0316, OR 0.9998, 95% CI [0.9996, 0.99998]). In the three groups, the risk of developing NVG associated with elevated levels of TGF-β (P < 0.001, OR 1.04, 95% CI [1.02, 1.05]). ConclusionsThe levels of these eight cytokines in the aqueous humor increased with the severity of diabetic retinopathy, especially in NVG-PDR. This study suggests that TGF-β, ICAM-1, IL-10, VEGF, and VCAM-1 may play a role in the progression of diabetic retinopathy, especially TGF-β, which may plays a significant role in NVG-PDR. These cytokines potentially may be used as biomarkers to predict the progress of diabetic retinopathy, contribute to the choice of treatment options and/or monitor treatment responses.