García-Quintans, NievesSánchez-Ramos, CristinaPrieto, IgnacioTierrez, AlbertoArza, ElviraAlfranca, ArantzazuRedondo, Juan MiguelMonsalve, María2024-01-312024-01-312016-04Angiogenesis. 2016 Apr;19(2):217-28.http://hdl.handle.net/20.500.12105/17393Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that is known to be inactivated in diabetic subjects. This study aimed to investigate the contribution of PGC-1α inactivation to the development of oxygen-induced retinopathy. We analyzed retinal vascular development in PGC-1α(-/-) mice. Retinal vasculature of PGC-1α(-/-) mice showed reduced pericyte coverage, a de-structured vascular plexus, and low perfusion. Exposure of PGC-1α(-/-) mice to hyperoxia during retinal vascular development exacerbated these vascular abnormalities, with extensive retinal hemorrhaging and highly unstructured areas as compared with wild-type mice. Structural analysis demonstrated a reduction in membrane-bound VE-cadherin, which was suggestive of defective intercellular junctions. Interestingly, PGC-1α(-/-) retinas showed a constitutive activation of the VEGF-A signaling pathway. This phenotype could be partially reversed by antioxidant administration, indicating that elevated production of ROS in the absence of PGC-1α could be a relevant factor in the alteration of the VEGF-A signaling pathway. Collectively, our findings suggest that PGC-1α control of ROS homeostasis plays an important role in the regulation of de novo angiogenesis and is required for vascular stability.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Oxidative StressAnimalsBlood VesselsMice, Inbred C57BLOxygenPerfusionPericytesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRetinaRetinal DiseasesAttribution-NonCommercial-NoDerivatives 4.0 Internacional2695147819221710.1007/s10456-016-9502-01573-7209Angiogenesisopen access