Inflammatory and Angiogenic Factors in the Aqueous Humor and the Relationship to Diabetic Retinopathy

Abstract

Purpose: To determine the relationship between the aqueous concentrations of inflammatory and angiogenic factors and the severity of diabetic retinopathy and diabetic macular edema. Methods: Aqueous samples were obtained from 50 eyes of diabetic patients and 28 eyes of nondiabetic subjects. The aqueous levels of inflammatory factors, including IL-1 beta, TNF-alpha, MCP-1, IP-10, IL-8, IL-6, and VEGF were measured with multiplex bead array assays. The aqueous levels of cytokines were investigated according to the severity of diabetic retinopathy and diabetic macular edema measured by optical coherence tomography. Results: The aqueous levels of MCP-1, IP-10, IL-8, and VEGF were higher in eyes of diabetic patients than in eyes of nondiabetic subjects. The aqueous levels of MCP-1 and IP-10 were elevated in eyes with severe NPDR and PDR compared to eyes with less severe DR and eyes of nondiabetic subjects. There was a trend toward elevated IL-8 levels in eyes with severe NPDR compared to eyes of nondiabetic subjects. The aqueous levels of VEGF were markedly elevated in eyes with PDR that had not received PRP compared to eyes with severe NPDR. Eyes with PDR that had received PRP treatment showed higher MCP-1 and IP-10 levels than eyes with PDR that had not received PRP treatment. The aqueous levels of IL-6 were positively correlated with TMV and CSMT in eyes with DR. Conclusions: Elevation of MCP-1, IP-10, and IL-8 levels in eyes with severe NPDR suggests that inflammatory change precedes the development of neovascularization in PDR. The positive correlation between the aqueous levels of IL-6 and macular thickness indicates that IL-6 may play a central role in the development of diabetic macular edema.