Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy

Clinical studies have shown a relationship between diabetic retinopathy and Vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complicatio ns, including diabetic retinopathy. N-epsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In thi s study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML ACE, and CML concentrations in aqueous humor and serum were then compared w ith the severity of diabetic retinopathy, Immunohistochemical detection ana lysis of non-CML ACE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non -CML ACE and CML increased along with the progression of diabetic retinopat hy compared to age-matched controls. After coagulation therapy, the VEGF, n on-CML AGE, and CML levels were significantly reduced. Immunostaining showe d diffuse co-localization of non-CML ACE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidati on reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.