**1. Introduction**

In recent years emerging evidence has indicated that glucagon-like peptide 1 (GLP-1) exerts beneficial effects in experimental diabetic retinopathy (DR) [1–4]. The underlying mechanisms involve a downregulation of vascular endothelial growth factor (VEGF), proinflammatory cytokines and proapoptotic signaling, reduction of the excitotoxicity mediated by glutamate and a protective role for the tight junctions and cells of the blood-retinal barrier [1–4]. However, little is known regarding he effect of GLP-1 on oxidative stress.

Oxidative stress as a result of chronic hyperglycemia play a key role in diabetic complications, including DR [5]. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are physiologically produced and are needed for redox signaling, but they can also alter the normal cellular homeostasis. For this reason, a precise balance between ROS/RNS production and antioxidant activity is required [6]. The retina is more susceptible to oxidative events than other tissues due to high oxygen uptake and glucose oxidation. In fact, it has been shown that diabetic patients present lower activity of antioxidant

enzymes (superoxide dismutase (SOD), glutathione reductase and glutathione peroxidase) and high ROS/RNS levels in the retina [7,8]. Recent experimental evidence suggests that oxidative stress not only contributes to the DR development, but also causes resistance to the beneficial effects of good glycemic control [9].

The aim of this study was to investigate the antioxidant and antinitrosative properties of topical GLP-1 in an experimental model of DR.
