Vitreous Levels of VEGF and SDF-1 in Patients with Diabetic Retinopathy

Abstract

Abstract: : Purpose: Proliferative diabetic retinopathy (PDR), the leading cause of adult blindness, is characterized by aberrant neovascularization (NV). Endothelial cell precursors circulate in the bloodstream, are recruited to sites of neoangiogenesis and participate in new blood vessel formation. These precursors express the chemokine receptor CXCR4 and migrate in response to stromal derived factor (SDF-1), a highly conserved member of the CXC chemokine family. SDF-1 is a potent stimulator of vascular endothelial growth factor (VEGF) expression, the main effector of retinal NV. We proposed to investigate the relationship between SDF-1 and VEGF in the vitreous fluid of diabetic patients with varying degrees of diabetic retinopathy and cystoid macular edema (CME) before and after intraocular injection of Triamcinolone. Methods: In this prospective study, 40 patients were included. 27 eyes were classified as nonproliferative diabetic retinopathy (NPDR), 11 eyes were classified as inactive proliferative diabetic retinopathy (PDR) with CME, 12 eyes with mild PDR with or without CME, 20 eyes with florid PDR with or without CME, and 9 eyes with neovascular glaucoma (NVG) or NV of the iris (NVI). Vitreous (0.5-0.6 ml) was obtained prior to injection of Triamcinolone 4 mg. VEGF and SDF-1 were measured by ELISA. Results: Vitreous levels of both VEGF and SDF-1 were significantly higher (p<0.01) in diabetic patients with PDR (VEGF: 303-2,722 ng/ml; SDF-1: 120-300 pg/ml) than in patients with NPDR (VEGF: 235±47.3 ng/ml; SDF-1: 95±29.7 pg/ml). SDF-1 levels were markedly increased in patients with CME (70±18.7 pg/ml) compared to those without (35±13.6 pg/ml). Triamcinolone administration resulted in the dramatic reduction of VEGF and SDF-1 to nearly undetectable levels. Triamcinolone eliminated CME, NVI and caused regression of active NV and the initiation of fibrosis. Conclusions: Elevated SDF-1 is associated with the presence of CME and is reduced by Triamcinolone. The elimination of CME and NVI, as well as the regression of active neovascularization and the initiation of fibrosis by Triamcinolone may be due to the suppression of VEGF and SDF-1. Our results support a role for SDF-1 and VEGF in the pathogenesis of diabetic retinopathy.

Keywords: diabetic retinopathy • neovascularization • drug toxicity/drug effects