Mesenchymal stem cell-conditioned medium attenuates the retinal pathology in amyloid-β-induced rat model of Alzheimer's disease: Underlying mechanisms.

Abstract

Amyloid-beta (Aβ) oligomer is known to contribute to the pathophysiology of age-related macular degeneration. Herein, we aimed to elucidate the in vivo and in vitro effects of Aβ_1-42 application on retinal morphology in rats. Our in vivo studies revealed that intracerebroventricular administration of Aβ_1-42 oligomer caused dysmorphological changes in both retinal ganglion cells and retinal pigment epithelium. In addition, in vitro studies revealed that ARPE-19 cells following Aβ_1-42 oligomer application had decreased viability along with apoptosis and decreased expression of the tight junction proteins, increased expression of both phosphor-AKT and phosphor-GSK3β and decreased expression of both SIRT1 and β-catenin. Application of conditioned medium (CM) obtained from mesenchymal stem cells (MSC) protected against Aβ_1-42 oligomer-induced retinal pathology in both rats and ARPE-19 cells. In order to explore the potential role of peptides secreted from the MSCs, we applied mass spectrometry to compare the peptidomics profiles of the MSC-CM. Gene ontology enrichment analysis and String analysis were performed to explore the differentially expressed peptides by predicting the functions of their precursor proteins. Bioinformatics analysis showed that 3-8 out of 155-163 proteins in the MSC-CM maybe associated with SIRT1/pAKT/pGSK3β/β-catenin, tight junction proteins, and apoptosis pathway. In particular, the secretomes information on the MSC-CM may be helpful for the prevention and treatment of retinal pathology in age-related macular degeneration.