Resveratrol ameliorates disorders of mitochondrial biogenesis and dynamics in a rat chronic ocular hypertension model

Abstract Aims To explore the roles of mitochondrial biogenesis and dynamics in both RGC-5 cells apoptosis and rat retinal damage induced by elevated pressure and their involvement in resveratrol (RSV)-induced cell protection. Materials and methods The chronic ocular hypertension (COH) model was established in rats by injecting superparamagnetic iron oxide into anterior chamber. The RGC-5 cells were incubated under ambient and elevated pressure (70 mm Hg) respectively. The intraocular pressure (IOP) was measured using a handheld Tonolab tonometer; mitochondrial dysfunction was analyzed by membrane potential (MMP) depolarization, reactive oxygen species (ROS) level and transmission electron microscope (TEM) detection. Annexin V/PI staining and the terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay were performed for apoptosis detection. Hematoxylin–Eosin staining was performed for retinal morphology detection. The expression of mitochondrial biogenesis and dynamics relating proteins were analyzed by western blot. Key findings The retinal morphology and mitochondrial function deteriorated in chronic ocular hypertension (COH) rats. The cells showed apoptosis and mitochondrial dysfunction under elevated pressure (70 mm Hg) incubation. Upregulating AMPK, NRF-1, Tfam, mfn-2, OPA1 expression with RSV-treatment could decrease the cell apoptosis, mitochondrial membrane potential depolarization, ROS generation both in in vitro and in vivo experiments, and normalized the retinal morphology in vivo. Significance Both in vitro and in vivo experiments demonstrated that activated AMPK/PGC-1α signaling pathway and improved expression of proteins were related to mitochondrial dynamics could be the possible mechanism underlying in the RSV's mitochondrial protection.