Protective effect of Nitro-Oleic Acids in neovascularization and neurodegeneration in Oxygen-Induced Retinopathy mouse model

VAGLIENTI, MARIA V.; SUBIRADA, PAULA V.; PAZ, MARÍA C.; BONACCI, GUSTAVO; SÁNCHEZ, MARÍA C.

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Jornada; III Jornadas Avances en Medicina Traslacional IUCBC 2022. Centro de Investigación en Medicina Traslacional Severo Amuchástegui (CIMETSA) y Secretaría de Investigación del IUCBC.; 2022

Centro de Investigación en Medicina Traslacional Severo Amuchástegui (CIMETSA) y Secretaría de Investigación del IUCBC

Inflammation, oxidative and nitrosative stress are involved in NeovascularRetinopathies (NR). Nitro-fatty acids are important electrophilicsignaling mediators with anti-inflammatory, antioxidant andcytoprotective properties (Keap1/Nrf2 pathway). Hence, our goalwas to evaluate the effect of Nitro-oleic acid (NO2-OA) in a validatedoxygen-induced retinopathy mouse model (OIR). Briefly, C57BL/6mice were exposed to 75% O2 from P7 to P12, after that they werebrought to room air (RA) for additional five (P17) days or nine days(P26). Age-match mice in RA were used as controls. Some OIR micewere i.o. injected at P12 with 5 μM of NO2-OA or vehicle and i.p. atP14, P17, P20, P23 with 15 mg/Kg of NO2-OA or vehicle. At P17 orP26 mice were sacrificed. Some eyes were fixed to obtain retinalwhole mount for microscopy or cryosection and other retinas wereused to analyze protein expression by Western blot or RT-PCR. Theretinal functionality was measured by scotopic electroretinography(ERG). Amplitudes and latencies of a- and b-waves from scotopicERG were recorded at P17 y P26. The whole mount showed thatNO2-OA induced the vascular regrowth and decrease the pathologicalneovascularization and vaso-obliteration at P17. Interestingly,RT-PCR revealed a significant increase in VEGF levels in OIR micerespect to RA mice, but not difference was found between NO2-OAtreatment and vehicle. In addition, Western blot of neural retinasshowed significant changes in proteins involved in neurotoxicity andglial stress such as GS and GFAP at P17 and P26 in OIR micetreated with NO2-OA respect to vehicle. No differences in ERG signalswere observed between mice injected with vehicle or NO2-OAat P17. However, NO2-OA prevented the decrease in b-wave amplitudeat P26. Correlating with a decrease in the caspase 3 total levelat P26 OIR NO2-OA prevented this decrease. Overall, these findingssuggest that NO2-OA Have multiple benefits for retinal cells in NR.