CONICET | Buscador de Institutos y Recursos Humanos

Inflammation, oxidative and nitrosative stress are involved in Neovascular Retinopathies (NR). Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory, antioxidant and cytoprotective properties (Keap1/Nrf2 pathway). Hence, our goal was to evaluate the effect of Nitro-oleic acid (NO2-OA) in a validated oxygen-induced retinopathy mouse model (OIR). Briefly, C57BL/6 mice were exposed to 75% O2 from P7 to P12, after that they were brought to room air (RA) for additional five (P17) days or nine days (P26). Age-match mice in RA were used as controls. Some OIR mice were i.o. injected at P12 with 5 μM of NO2-OA or vehicle and i.p. at P14, P17, P20, P23 with 15 mg/Kg of NO2-OA or vehicle. At P17 or P26 mice were sacrificed. Some eyes were fixed to obtain retinal whole mount for microscopy or cryosection and other retinas were used to analyze protein expression by Western blot or RT-PCR. The retinal functionality was measured by scotopic electroretinography (ERG). Amplitudes and latencies of a- and b-waves from scotopic ERG were recorded at P17 y P26. The whole mount showed that NO2-OA induced the vascular regrowth and decrease the pathological neovascularization and vaso-obliteration at P17. Interestingly, RT-PCR revealed a significant increase in VEGF levels in OIR mice respect to RA mice, but not difference was found between NO2-OA treatment and vehicle. In addition, Western blot of neural retinas showed significant changes in proteins involved in neurotoxicity and glial stress such as GS and GFAP at P17 and P26 in OIR mice treated with NO2-OA respect to vehicle. No differences in ERG signals were observed between mice injected with vehicle or NO2-OA at P17. However, NO2-OA prevented the decrease in b-wave amplitude at P26. Correlating with a decrease in the caspase 3 total level at P26 OIR NO2-OA prevented this decrease. Overall, these findings suggest that NO2-OA Have multiple benefits for retinal cells in NR.