Effect of nitro-oleic acids in mouse model of oxygen-induced retinopathy

VAGLIENTI MV; RIDANO MAGALI E; SANCHEZ MC; SUBIRADA CALDARONE PAULA; BARCELONA PF; PAZ MC; BONACCI GR

Congreso; XXXIV Congreso Anual de Sociedad Argentina de Investigación en Neurociencias; 2019

Inflammation, oxidative and nitrosative stress are involved in Neovascularretinopathies (NR). Although, VEGF inhibitors have been established as themainstay of current treatment, the clinical benefits have not always beensuccessful. Moreover, Nitro-fatty acids are important electrophilic signalingmediators with anti-inflammatory and cytoprotective properties (Keap1/Nrf2pathway). Here, we hypothesized that Nitro-oleic acid (NO2-OA) can modulate theantioxidant response in NR. Initially, intraocular (i.o.) and intraperitoneal (i.p.)injection of NO2-OA toxicity was assessed by scotopic electroretinography (ERG)and H&Eo staining. C57BL/6 adult mice were i.o. injected at P0 with PBS, vehicleand 5μM of NO2-OA, and i.p. at P2, P5, P8, P11 and P14 with PBS, vehicle and15 mg/Kg of NO2-OA. The a- and b-waves from ERG were recorded at P3, P7 andP15. No differences in ERG signals were observed. Thus, the Oxygen-InducedRetinopathy (OIR) model was carried out. Briefly, C57BL/6 mice were exposed to75% O2 from P7 to P12, and then brought to room air for additional five (P17) ornine days (P26). Some OIR mice were i.o. injected at P12 with 5 μM of NO2-OA orvehicle and i.p. at P14, P17, P20 and P23 with 15 mg/Kg or vehicle. Western blotof neural retinas showed significant changes in glutamine synthetase, VEGF-A andGFAP levels at P17 and P26 in OIR mice treated with NO2-OA respect to vehicle.These findings indicate that NO2-OA could be beneficial for retinal cells in the NR.