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

VAGLIENTI, MV; SUBIRADA, PV; PAZ, MC; RIDANO, ME; BARCELONA, P; BONACCI, GR; SANCHEZ, MC

Carlos Paz

Congreso; SAN 2019 (XXXIV Congreso Anual de Sociedad Argentina de Investigación en Neurociencias.; 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

Inflammation, oxidative and nitrosative stress are involved in Neovascular retinopathies (NR). Although, VEGFinhibitors have been established as the mainstay of current treatment, the clinical benefits have not alwaysbeen successful. Moreover, Nitro-fatty acids are important electrophilic signaling mediators with antiinflammatory and cytoprotective properties (Keap1/Nrf2 pathway). Here, we hypothesized that Nitro-oleic acid(NO2-OA) can modulate the antioxidant 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/6adult mice were i.o. injected at P0 with PBS, vehicle and 5μM of NO2-OA, and i.p. at P2, P5, P8, P11 and P14 withPBS, vehicle and 15 mg/Kg of NO2-OA. The a- and b-waves from ERG were recorded at P3, P7 and P15. Nodifferences in ERG signals were observed. Thus, the Oxygen-Induced Retinopathy (OIR) model was carried out.Briefly, C57BL/6 mice were exposed to 75% O2 from P7 to P12, and then brought to room air for additional five(P17) or nine days (P26). Some OIR mice were i.o. injected at P12 with 5 μM of NO2-OA or vehicle and i.p. atP14, P17, P20 and P23 with 15 mg/Kg or vehicle. Western blot of neural retinas showed significant changes inglutamine synthetase, VEGF-A and GFAP levels at P17 and P26 in OIR mice treated with NO2-OA respect tovehicle. These findings indicate that NO2-OA could be beneficial for retinal cells in the NR.