LAUSR

The important role of neurodegeneration in the pathogenesis of diabetic retinal disease (DRD) and the evidence that several neuroprotective retinal factors are downregulated in diabetes have led to propose replacement treatment via eyedrops of these neuroprotective factors as a new therapeutic strategy [1, 2]. Glucagon-like peptide-1 (GLP-1) is one of them; however, it presents low stability and rapid degradation by dipeptidyl peptidase-4 (DPP-4), which is more abundant in diabetic than in non-diabetic retina [2]. To overcome this issue, the use of topical administration of DPP-4 inhibitors (DPP-4i) has been proposed [2]. These drugs not only reproduce the positive GLP-1 effects but even have other beneficial actions unrelated to GLP-1R activation that should be elucidated. This study examines for the first time whether sitagliptin (a DPP-4i), in absence of GLP-1, prevents hyperpermeability on the cells forming the outer and inner blood-retinal barrier (BRB) under conditions that simulate the diabetic milieu . For that purpose, ARPE-19 and human retinal endothelial cells (HREC), were cultured and exposed to five experimental conditions for three days: a) Physiological condition (5.5 mmol/L D-glucose), b) High glucose condition (25 mmol/L D-glucose); c