Mesenchymal stem cell-derived exosomes mitigate amyloid β-induced retinal toxicity: Insights from rat model and cellular studies

Abstract

Amyloid β (Aβ) has emerged as a pathophysiological driver in age-related macular degeneration (AMD), emphasizing its significance in the aetiology of this prevalent sight-threatening condition. The multifaceted nature of AMD pathophysiology, presumably involving diverse retinal cascades, corresponds with the complexity of Aβ-induced retinopathy. Therefore, targeting a broad array of pathogenic processes holds promise for therapeutic intervention in AMD-associated retinal pathology. This study investigates the potential of exosomes derived from adipose tissue mesenchymal stem cells (AT-MSC-Exosomes) in alleviating Aβ-induced retinotoxicity. Through intravitreal injections in wild-type rats and RPE-like cell culture experiments, we examined the protective effects of AT-MSC-Exosomes against Aβ42 retinotoxicity. Our findings reveal that pre-treatment with AT-MSC-Exosomes enabled nearly-intact retinal function in vivo and maintained retinal cell viability in vitro, evidenced by longitudinal electroretinography (ERG) and XTT proliferation assays, respectively. Fluorescent labelling demonstrated increased migration of AT-MSC-Exosomes towards retinal cells under conditions of amyloid-related toxicity. Proteomic analysis indicated a decrease in the retinal levels of heat-shock proteins activated by pathogenic Aβ fibrils following AT-MSC-Exosome treatment. Similarly, immunostaining highlighted the modulation of α-crystallin expression in retinal astrocytes by AT-MSC-Exosomes. These results suggest the potential therapeutic relevance of AT-MSC-Exosomes in Aβ-related retinal pathology, offering a promising avenue for future AMD treatment strategies.