CONICET | Buscador de Institutos y Recursos Humanos

Proliferative retinopathies are among leading causes of irreversible blindness. Inflammation, oxidative and nitrosative stress are involved in the pathogenesis of diabetic complications, including retinopathy.mAlthough, vascular endothelial growth factor (VEGF). Inhibitors have been established as the mainstay of current treatment, the clinical benefits have not always been successful in preserving retinal function. In this regard, we hypothesized that Keap1/Nrf2 pathway can modulate the antioxidant response in neovascular retinopathies. For this reason, we used the activating Keap1/Nrf2 nitro fatty acid (NO2-FA), which are important electrophilic signaling mediators with anti-inflammatory and cytoprotective activities. Due to Muller Glial Cells (MGCs) are commanding survival and death in retina, we studied the effect of nitro-oleic acid in the human MGC line, MIO-M1. Initially, cell viability was assessed by MTT assays. MIO-M1 cells exposed to 0.1; 1.0; 2.5; 5.0 or 10 M NO2-OA during 24 to 72 h showed no significant reduction in cell viability (p0,5). Results are expressed as percentage of cell viability relative to 0.1% v/v vehicle (methanol). On the other hand, the ability of MIO-M1 cells to respond to a No2-OA stimulus was evaluated through the increase of antioxidant enzymes such as hemo-oxygenase 1(HO-1). MIO-M1 cells were stimulated with NO2-OA, and the expression of HO-1 was measured by WB at 8 and 16 h post-stimulus. The results showed a significant increase of HO-1 with 5 M of NO2-OA at 8 h post-stimulus (p0.05). To determine whether NO2-OA could be beneficial for retinal cells against oxidative stress, we treated MIO-M1 cells with H2O2 (50-200 mol/l). Preliminary results showed that NO2-OA reduced H2O2 damage. Thus, NO2-OA may act as an antioxidant protecting retinal cells from oxidative damage. At present, to corroborate this effect in an in vivo model, we are evaluating NO2-OA in an oxygen-induced retinopathy mouse model.