Inhibition of Diabetic Leukostasis and Blood–Retinal Barrier Breakdown With a Soluble Form of a Receptor for Advanced Glycation End Products

Abstract

Abstract: : Purpose: The interaction of advanced glycation end products (AGE) with their receptors is hypothesized to be involved in the development of diabetic retinopathy. However, there are no direct data showing the involvement of AGE receptors in diabetic retinopathy. In the present study, we analyzed the role of an AGE receptor, receptor for AGE (RAGE), in the development of the diabetic retinopathy in vivo. Methods: C57/BJ6 male mice were made diabetic with intraperitoneal injection of streptozocin. Three months following the onset of diabetes, the soluble form of RAGE (sRAGE) or mouse serum albumin was injected intraperitoneally at 20 microgram/day for fourteen days. After the final injection, blood–retinal barrier breakdown and retinal leukostasis were quantified. Results: Experimental diabetes was associated with blood–retinal barrier breakdown and the leukostasis in the C57/BJ6 mice. The blood–retinal barrier breakdown and leukostasis in the diabetic C57/BJ6 mice were accompanied by the increased expression of VEGF and ICAM–1 in the retina. The systemic administration of sRAGE significantly inhibited the blood–retinal barrier breakdown and the leukostasis in diabetic mice. Conclusions: These data indicate that AGEs induced blood–retinal barrier breakdown and the retinal leukostasis, which are characteristic clinical symptoms of diabetic retinopathy. Furthermore, these data demonstrate that blocking AGE bioactivity can be used for the treatment of diabetic retinopathy.

Keywords: diabetic retinopathy • glycoconjugates/glycoproteins