A comparative study of the effectivity of MSC-based, NP-based and combined therapies in an experimental model of NaIO3-induced retinal degeneration

Background

Mesenchymal stem cells (MSCs) are currently tested as one of the promising options for the therapy of retinal diseases, due to their immunomodulatory and neuroprotective abilities. However, there are several limitations associated with this type of treatment. Therefore, combinations of MSCs with other therapeutic agents are being considered. One of such approaches is represented by the application of MSCs with nanoparticles (NPs), which are widely used in medicine for their antimicrobial and immunomodulatory properties. Nevertheless, there is a possibility of negative effects of NPs on MSCs.

Methods

In this study, we tested the in vitro and in vivo effect of silver (Ag) NPs on the properties of MSCs in an experimental mouse model of chronic retinal degeneration induced by sodium iodate.

Results

The results showed that simultaneous intravitreal administration of MSCs with AgNPs had no effect on the survival of MSCs in the eye, but a less effective regulation of Iba-1 (activated microglia/macrophages) and interleukin-1β expression in the retinal tissue compared to MSCs or AgNP only treated groups was observed. However, all treated groups had decreased expression of the gene for galectin-3 compared to the untreated control. In addition, MSCs applied alone or in combination with AgNPs and sorted from the degenerated retina on day 7 after application had increased expression of genes for specific retinal markers, and for transforming growth factor-β and insulin-like growth factor-1 compared to untreated naïve MSCs. On the contrary, the increased expression of the gene for glial cell-derived growth factor was observed only in the MSCs combined with AgNPs. However, the application of MSCs with AgNPs triggered increased expression for the IL-6 gene in the CD45 cells separated from the retina.

Conclusion

Overall, the results show that the application of MSCs or AgNPs has an immunomodulatory effect in chronic retinal degeneration, but the combined application of MSCs and AgNPs could decrease the effects of a single therapy.