Protective Role of Bone Marrow Mesenchymal Stem Cells (BMSCs) in Repairing Epithelial Cells of Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is one of the main causes of blindness. By directly employing mesenchymal stem cells to repair damaged retinal tissues, we aim to study the underlying repair mechanisms. 30 DR patients were included, along with 30 healthy control cases. Western-blot and qRT-PCR were conducted to measure PI3K/Akt pathway-related genes. The PI3K/Akt antagonist (Rigosertib) was utilized in the induction process of cell differentiation to analyze the effects of PI3K/Akt pathwayspecific proteins and mRNAs. DR patients showed significantly elevated expression of PI3K/Akt compared to control. With prolongation of induction, the expression of normal epithelial cell-related genes (SpC, SpB, SpA, CK18, KGF and Occludin) was elevated along with upregulated Occludin and KGF, two specific proteins of healthy epithelial cells. Meanwhile, the quantities of Occludin and KGF in cell culture medium showed a gradual downward trend. In the differentiation of BMSCs towards epithelial cells, addition of PI3K/Akt antagonist Rigosertib was negatively correlated with the expression of several genes (IGF-1, shh, EGF, mTOR, AKT and PI3K) and decreased the quantities of PI3K/Akt pathway-specific proteins (mTOR, PI3K and AKT). In conclusion, BMSCs can effectively reduce the release of cytokines in DR and promote the repair of damaged diabetic retina, possibly through regulation of PI3K/Akt signaling pathway.