Stem cells ameliorate neurotrauma-induced visual disturbances and retinopathy via broad normalization of the β-catenin-related signaling pathway

Abstract

Abstract To determine the mechanisms underlying the beneficial effects of mesenchymal stem cells (MSC) on brain trauma-induced retinopathy both in vivo and in vitro. Repeated traumatic brain injury (TBI) was induced by lateral fluid percussion in adult male Wistar rats under general anesthesia. The sham and TBI groups received an intravenous dose of normal saline (1 mL/kg of body weight) or MSC (4 × 106 cells/ml/kg) on day 3 after surgery, respectively. The visual cliff method and modified neurological severity score were used to test the visual and neurobehavioral function of rats. Thirty-five days after TBI, rats were euthanized, and histochemical analyses were conducted. Cultured R28 cells were subjected to a stretch injury (SI) and then cocultured with MSC. The R28 cell viability, apoptosis, mitochondria membrane potential, radical oxygen species (ROS) generation, protein signaling, and growth factors composition were measured. Rats, 35 days post-TBI, displayed both visual disturbances and neurobehavioral deficits. Simultaneously, reduced RGC layer thickness, decreased cell numbers, increased RGC apoptosis, and decreased b-catenin-containing neurons were noted. Our in vitro studies further demonstrated that SI caused reduced cell viability, neuronal apoptosis and autophagy, mitochondria distress, increased intracellular ROS contents, and decreased b-catenin expression in cultured R28. Intravenous administration of MSC significantly ameliorated the visual disturbance and retinopathies in TBI rats. Topical application of MSC significantly attenuated stretch injury-induced cell stress responses in cultured RGC. MSC therapy might ameliorate visual disturbances and retinopathies in rats with neurotrauma via broad normalization of retinal b-catenin-related signaling pathways.