Fig. 6: The schematic diagram shows the action mechanism of everolimus pretreatment, which regulates GLUT3 membrane trafficking and mitochondrial anti-oxidation in UCB-MSCs under high glucose conditions.

Two types of UCB-MSCs were transplanted subconjunctivally into a rat model of STZ-induced diabetic retinopathy. When UCB-MSCs alone were injected, activated mTORC1 signaling in high glucose conditions increased cofilin phosphorylation, which in turn elongated actin filaments and upregulated the membrane trafficking of GLUT3. The increased membrane expression of GLUT3 allows more glucose to enter the cells, leading to mtROS overproduction. UCB-MSCs pretreated with everolimus inhibited mTORC1 signaling in a high glucose environment, resulting in actin depolymerization via cofilin. Reduced membrane trafficking of GLUT3 results in a reduced intracellular glucose influx, which alleviates mtROS production. In other words, the anti-apoptotic effect of everolimus accelerated retinal tissue and function recovery by UCB-MSCs.