Hyperoxia induces glutamine-fuelled anaplerosis in retinal Müller cells

Premature infants require oxygen supplementation to survive, but excess oxygen causes retinovascular growth suppression that underlies the leading cause of infant blindness known as retinopathy of prematurity (ROP). We analyzed changes in intermediary metabolism during hyperoxia in human retinal endothelial cells (RECs) and human retinal Müller glia, which coexist through glutamine consumption and production, respectively. Using a stable isotope labeling technique in human RECs and human Müller cells in culture, here we show that Müller cells in hyperoxia block entry of glycolytic carbon into the tricarboxylic acid (TCA) cycle and instead oxidize glutamine. In hyperoxia, catabolism of glutamine increased ammonium release by 2-fold. Hyperoxia induces glutamine-fueled anaplerosis that reverses basal Müller cell metabolism from production to consumption of glutamine.