Microvessels are composed of endothelial cells and pericytes. We have previously shown that
advanced glycation end products (AGE) not only inhibit
DNA synthesis but also induce apoptosis in cultured
retinal pericytes, thereby being involved in pericyte loss, the earliest histopathological hallmark of
diabetic retinopathy. Since pericytes play a central role in the maintenance of microvascular homeostasis in the retina, blockade of the harmful effects of AGE on
retinal pericytes may become a novel therapeutic strategy for the treatment of
diabetic retinopathy. In this study, we selected
DNA aptamers directed against AGE in vitro and then examined their cytoprotective effects on AGE-exposed
retinal pericytes. We identified 15
DNA aptamers directed against AGE-
human serum albumin using combinatorial chemistry techniques in vitro. Structural analysis revealed that they had bulge-loop structures with
cytosine-rich sequences. All of the aptamers, but not non-binding control aptamers, were found to inhibit the AGE-induced decrease in
DNA synthesis as well as apoptotic cell death in pericytes. Among the selected aptamers, the clone 9 aptamer completely blocked the toxic effects of AGE, and its dissociation constant was 1 micromol/L. These results indicate that
DNA aptamers are a useful tool for inhibiting the cytotoxic effects of AGE on cultured
retinal pericytes. Our study suggests that blockade of the AGE effects by
DNA aptamers may lead to a novel therapeutic strategy for the treatment of
diabetic retinopathy.