Exosomes derived from mesenchymal stem cells attenuate Amyloid β toxicity in rat retina

Abstract

Purpose : Age-related macular degeneration (AMD) poses a complex pathogenesis with unclear underlying molecular mechanisms. Previous studies have highlighted the presence of Amyloid β (Aβ) in drusen, suggesting the involvement of this group of neurotoxic peptides in the development of the disease. We previously demonstrated clear retinal pathogenicity of various Aβ species in rats. Recently, exosomes derived from mesenchymal stem cells sourced from adipose tissue (AT-MSC-Exosomes) have shown promise in neurodegenerative states such as Alzheimer’s disease given their ability to modulate inflammation and provide trophic support. Such an approach could be beneficial in retinal pathology related to Aβ. This study explored the efficacy of AT-MSC-Exosomes in ameliorating Aβ-induced retinotoxicity

Methods : Wild-type rats were treated with intravitreal injections (10µl) of AT-MSC-Exosomes in one eye 5 days prior to injection of fibrillar Aβ42 assemblies into both eyes. Retinal function was assessed by electroretinography (ERG) at baseline, following AT-MSC-Exosome injection, and through 28 days after Aβ administration. ARPE-19 cells were treated with AT-MSC-Exosomes for 1hr before exposure to fibrillar Aβ42 for 18hrs. Cell viability was determined by the XTT proliferation assay. Fluorescent-labelling of AT-MSC-Exosomes was employed to track their cellular uptake under conditions of amyloid-related toxicity

Results : ERG responses in rat eyes treated with AT-MSC-Exosomes prior to administration of toxic fibrillar Aβ42 assemblies were nearly intact compared to controls. The amplitudes of the ERG a-wave and b-wave were close to normal, while those obtained from control eyes treated with Aβ42 assemblies alone showed significant reductions. No retinal damage was observed in eyes treated solely with the AT-MSC-Exosomes. Moreover, AT-MSC-Exosomes protected ARPE-19 cells from Aβ42-induced toxicity. Compared with controls, AT-MSC-Exosomes exhibited increased migration in cell cultures which were exposed to the toxic Aβ42 fibrils

Conclusions : Our results provide evidence that AT-MSC-Exosomes provide robust protection against Aβ-mediated retinotoxicity in vivo and in vitro. Successful migration and uptake of exosomes was observed in the context of amyloid-mediated injury. Such insights hint at the potential relevance of AT-MSC-Exosomes in treatment of retinal pathology associated with Aβ

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.