Protective Effect of NO2-OA on Oxidative Stress, Gliosis, and Pro-Angiogenic Response in Müller Glial Cells

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 3; p. 494
• Main Authors: Vaglienti, María V., Subirada, Paula V., Joray, Mariana B., Bonacci, Gustavo, Sánchez, María C.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 02.02.2023; MDPI
• Subjects: Acetic acid; Angiogenesis; Antibodies; Antioxidants; Cytokines; Diabetic retinopathy; Endothelial cells; Extravasation; Fatty acids; Gene expression; Glial cells; Gliosis; Hypoxia; Inflammation; Infrared imaging systems; Ischemia; Lipopolysaccharides; Metabolism; Mueller cells; Müller glial cells; nitro-oleic acids; Nitrogen dioxide; Nrf2-Keap1 antioxidant pathway; Oleic acid; Oxidative stress; Phorbol 12-myristate 13-acetate; Plasma proteins; pro-angiogenic factor; Proteins; reactive oxygen species; Retina; Vascular endothelial growth factor; United States > US
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12030494

Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the blood–retinal barrier, with extravasation of plasma proteins such as α2-macroglobulin (α2M) and gliosis in Müller glial cells (MGCs, such as MIO-M1). It is well known that MGCs play important roles in healthy and sick retinas, including in PR. Nitro-fatty acids are electrophilic lipid mediators with anti-inflammatory and cytoprotective properties. Our aim was to investigate whether nitro-oleic acid (NO2-OA) is beneficial against oxidative stress, gliosis, and the pro-angiogenic response in MGCs. Pure synthetic NO2-OA increased HO-1 expression in a time- and concentration-dependent manner, which was abrogated by the Nrf2 inhibitor trigonelline. In response to phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), NO2-OA prevented the ROS increase and reduced the gliosis induced by α2M. Finally, when hypoxic MGCs were incubated with NO2-OA, the increase in VEGF mRNA expression was not affected, but under hypoxia and inflammation (IL-1β), NO2-OA significantly reduced VEGF mRNA levels. Furthermore, NO2-OA inhibited endothelial cell (BAEC) tubulogenesis. Our results highlight NO2-OA’s protective effect on oxidative damage, gliosis; and the exacerbated pro-angiogenic response in MGCs.