Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy
Inflammation and oxidative stress are involved in Proliferative Retinopathies (PR). Müller glial cells (MGCs) and microglia play pivotal roles in pathological neovascularization (NV) and neurodegeneration in PR. Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory...
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Elsevier
2025-06-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001478 |
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| author | Vaglienti María Victoria Paz María Constanza Gutierrez Maria Victoria Subirada Paula Virginia Luna Jose Bonacci Gustavo Sánchez María Cecilia |
| author_facet | Vaglienti María Victoria Paz María Constanza Gutierrez Maria Victoria Subirada Paula Virginia Luna Jose Bonacci Gustavo Sánchez María Cecilia |
| author_sort | Vaglienti María Victoria |
| collection | DOAJ |
| description | Inflammation and oxidative stress are involved in Proliferative Retinopathies (PR). Müller glial cells (MGCs) and microglia play pivotal roles in pathological neovascularization (NV) and neurodegeneration in PR. Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory and antioxidant properties. Herein, our goal was to evaluate the cytoprotective effect of nitro-oleic acid (NO2-OA) on neurons, MGCs and microglia in a mouse model of oxygen-induced retinopathy (OIR). NO2-OA induced vascular regrowth and reduced NV at P17 OIR, although no difference in the proangiogenic/antiangiogenic (VEGF-A/PEDF) balance was found between NO2-OA treatment and vehicle. In addition, Western blot and immunofluorescence assays showed that NO2-OA prevented gliosis at P17 OIR and decreased the number and activation of IBA1+ retinal myeloid cells. However, NO2-OA did not restore the decrease in expression of glutamine synthase (GS). Loss of retinal function in OIR mouse model measured by electroretinography was ameliorated, mainly at P26 OIR, after NO2-OA treatment. Western blot analysis of retinas from OIR mice revealed decreased levels of caspase-3 protein and increased number of TUNEL-positive cells at P26 compared to RA. Notably, these alterations were partially prevented after NO2-OA treatment. Besides, NO2-OA attenuates oxidative stress induced in MGCs exposed to aqueous humor from patients with different stages of PR. These findings highlight NO2-OA as a promising therapeutic strategy targeting both vascular and neuroglial components in PR, suggesting its potential clinical relevance. |
| format | Article |
| id | doaj-art-b4e1c96ffa47406f9d830e61bdfeebd9 |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-b4e1c96ffa47406f9d830e61bdfeebd92025-08-20T02:31:54ZengElsevierRedox Biology2213-23172025-06-018310363410.1016/j.redox.2025.103634Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathyVaglienti María Victoria0Paz María Constanza1Gutierrez Maria Victoria2Subirada Paula Virginia3Luna Jose4Bonacci Gustavo5Sánchez María Cecilia6Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, ArgentinaCentro Privado de Ojos Romagosa S.A, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, Argentina; Corresponding author. Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, 5000, Argentina; Corresponding author. Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba. Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000, Córdoba, Argentina.Inflammation and oxidative stress are involved in Proliferative Retinopathies (PR). Müller glial cells (MGCs) and microglia play pivotal roles in pathological neovascularization (NV) and neurodegeneration in PR. Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory and antioxidant properties. Herein, our goal was to evaluate the cytoprotective effect of nitro-oleic acid (NO2-OA) on neurons, MGCs and microglia in a mouse model of oxygen-induced retinopathy (OIR). NO2-OA induced vascular regrowth and reduced NV at P17 OIR, although no difference in the proangiogenic/antiangiogenic (VEGF-A/PEDF) balance was found between NO2-OA treatment and vehicle. In addition, Western blot and immunofluorescence assays showed that NO2-OA prevented gliosis at P17 OIR and decreased the number and activation of IBA1+ retinal myeloid cells. However, NO2-OA did not restore the decrease in expression of glutamine synthase (GS). Loss of retinal function in OIR mouse model measured by electroretinography was ameliorated, mainly at P26 OIR, after NO2-OA treatment. Western blot analysis of retinas from OIR mice revealed decreased levels of caspase-3 protein and increased number of TUNEL-positive cells at P26 compared to RA. Notably, these alterations were partially prevented after NO2-OA treatment. Besides, NO2-OA attenuates oxidative stress induced in MGCs exposed to aqueous humor from patients with different stages of PR. These findings highlight NO2-OA as a promising therapeutic strategy targeting both vascular and neuroglial components in PR, suggesting its potential clinical relevance.http://www.sciencedirect.com/science/article/pii/S2213231725001478Nitro-fatty acidsRetinal functionProliferative retinopathiesGliosisIBA1+ retinal myeloid cellsOxidative stress |
| spellingShingle | Vaglienti María Victoria Paz María Constanza Gutierrez Maria Victoria Subirada Paula Virginia Luna Jose Bonacci Gustavo Sánchez María Cecilia Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy Redox Biology Nitro-fatty acids Retinal function Proliferative retinopathies Gliosis IBA1+ retinal myeloid cells Oxidative stress |
| title | Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy |
| title_full | Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy |
| title_fullStr | Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy |
| title_full_unstemmed | Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy |
| title_short | Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy |
| title_sort | nitro oleic acid protects from neovascularization oxidative stress gliosis and neurodegeneration in oxygen induced retinopathy |
| topic | Nitro-fatty acids Retinal function Proliferative retinopathies Gliosis IBA1+ retinal myeloid cells Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001478 |
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