purpose. In all of the 8 diabetic human corneas, CML immunoreactivity was observed in the epithelial basement membrane area (arrowheads in A, B, C), whereas CML immunoreactivity was not found in the corresponding area in 7 of the 8 nondiabetic corneas (D). 2–5, 24/42) recruited from the pediatric outpatient clinic at Aker University Hospital were compared with 25 healthy nondiabetic control subjects. Animals were studied at 7 d, 3 wk, and 8 mo after induction of diabetes. Low-affinity binding sites specific for AGEs in the renal cortex (IC50 = 0.28 μM) were detected by in vitro autoradiography. RAGE expression is widespread in the retinal neuropile of rats and mice, being especially high in the Müller glia , and it has been shown to increase in diabetic rats concomitantly with ligands such as AGEs and S100b [6, 29]. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years.
AGE-treated wild-type mice showed a significant increase in inner retinal ischemia and a reduction in neovascularization compared with non-AGE controls (P < 0.001). Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered α-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro. First, it is possible that yet to be delineated mechanisms may cleave sRAGE from the endogenous full-length cell surface receptor. With duration of diabetes, the AGE contents increased significantly both in renal cortex and aorta. The excessive accumulation of AGEs was most apparent in the diabetic kidney. These findings suggest that the actual level of AGEs, in particular, in diabetic renal cortex is much higher than previously anticipated, and a newly developed enzyme-linked immunosorbent assay may be a powerful tool for investigating the role of the advanced Maillard reaction in the development of diabetic nephropathy.