Sodium iodate influences the apoptosis, proliferation and differentiation potential of radial glial cells in vitro

Abstract

Background/aims: Sodium iodate (NaIO3)-induced acute retinal injury is typically used as an animal model for degenerative retinal disease; however, how NaIO3 influences the apoptosis, proliferation and differentiation of endogenous retinal stem cells is unknown.

Methods: We exposed a radial glial cells (RGCs) line (L2.3) to different NaIO3 concentrations and determined the influence of NaIO3 on apoptosis, proliferation, and differentiation using flow cytometry and immunofluorescence assays. We used a real-time polymerase chain reaction assay to analyze the levels of mRNAs encoding GSK-3β, AXIN2, β-catenin, TGF-β1, SMAD2, SMAD3, NOG (Noggin), and BMP4.

Results: Cell density decreased dramatically as a function of the NaIO3 dose. NaIO3 increased apoptosis, inhibited mitosis, proliferation, and the Wnt/β-catenin pathway. CHIR99021 (Wnt agonist) treatment efficiently reversed the effects of NaIO3 on the apoptosis and proliferation of RGCs. The number of neuronal class III β-tubulin-positive cells decreased markedly, whereas that of glial fibrillary acidic protein-positive cells increased significantly when RGCs were exposed to NaIO3. During differentiation, the Nog mRNA level decreased and transforming growth factor-β1 (Tgf-β1) and Smad2/3 mRNA levels increased significantly when RGCs were exposed to NaIO3.

Conclusion: NaIO3 increased apoptosis, influenced the proliferation of RGCs and drove them toward astrocytic differentiation, likely through inhibition of the Wnt/β-catenin and noggin pathways and activation of the TGF-β1/SMAD2/3 pathway.