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Everolimus suppresses glucose transporter 3 membrane trafficking to improve therapeutic efficacy of umbilical cord blood-derived mesenchymal stem cell transplantation in diabetic retinopathy - PubMed

3 hours ago
  • #Diabetic Retinopathy
  • #Everolimus
  • #Stem Cell Therapy
  • Everolimus, an mTOR inhibitor, enhances the viability and function of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) under high glucose conditions typical of diabetic retinopathy (DR).
  • High glucose increases glucose uptake via GLUT3 overexpression, leading to excessive mitochondrial reactive oxygen species (mtROS) and cellular senescence in MSCs.
  • Everolimus reduces intracellular glucose levels and mtROS production by inhibiting mTORC1, which decreases actin stabilization and GLUT3 membrane translocation.
  • The down-regulation of cofilin phosphorylation by everolimus suppresses high glucose-induced glucose influx and mtROS generation.
  • In a streptozotocin-induced DR rat model, subconjunctival injection of GLUT3-knockdown or everolimus-pretreated UCB-MSCs improved retinal function compared to untreated groups.