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, co...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Journal of Extracellular Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jex2.70024 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832584458676469760 |
|---|---|
| author | Amanda Qarawani Efrat Naaman Rony Ben‐Zvi Elimelech Michal Harel Shahaf Sigal‐Dror Tali Ben‐Zur Tamar Ziv Daniel Offen Shiri Zayit‐Soudry |
| author_facet | Amanda Qarawani Efrat Naaman Rony Ben‐Zvi Elimelech Michal Harel Shahaf Sigal‐Dror Tali Ben‐Zur Tamar Ziv Daniel Offen Shiri Zayit‐Soudry |
| author_sort | Amanda Qarawani |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e90ddde587e44b9955a7311f4f48e96 |
| institution | Kabale University |
| issn | 2768-2811 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj-art-7e90ddde587e44b9955a7311f4f48e962025-01-27T13:48:44ZengWileyJournal of Extracellular Biology2768-28112025-01-0141n/an/a10.1002/jex2.70024Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studiesAmanda Qarawani0Efrat Naaman1Rony Ben‐Zvi Elimelech2Michal Harel3Shahaf Sigal‐Dror4Tali Ben‐Zur5Tamar Ziv6Daniel Offen7Shiri Zayit‐Soudry8Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa IsraelRuth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa IsraelRuth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa IsraelRuth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa IsraelRuth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa IsraelDepartment of Human Genetics and Biochemistry, School of Medicine, Felsenstein Medical Research Center Tel Aviv University Tel Aviv IsraelThe Smoler Proteomics Center Technion Israel Institute of Technology Haifa IsraelDepartment of Human Genetics and Biochemistry, School of Medicine, Felsenstein Medical Research Center Tel Aviv University Tel Aviv IsraelClinical Research Institute Rambam Health Care Campus Haifa IsraelAbstract 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.https://doi.org/10.1002/jex2.70024age‐related macular degenerationamyloid βmesenchymal exosomesretina |
| spellingShingle | Amanda Qarawani Efrat Naaman Rony Ben‐Zvi Elimelech Michal Harel Shahaf Sigal‐Dror Tali Ben‐Zur Tamar Ziv Daniel Offen Shiri Zayit‐Soudry Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies Journal of Extracellular Biology age‐related macular degeneration amyloid β mesenchymal exosomes retina |
| title | Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies |
| title_full | Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies |
| title_fullStr | Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies |
| title_full_unstemmed | Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies |
| title_short | Mesenchymal stem cell‐derived exosomes mitigate amyloid β‐induced retinal toxicity: Insights from rat model and cellular studies |
| title_sort | mesenchymal stem cell derived exosomes mitigate amyloid β induced retinal toxicity insights from rat model and cellular studies |
| topic | age‐related macular degeneration amyloid β mesenchymal exosomes retina |
| url | https://doi.org/10.1002/jex2.70024 |
| work_keys_str_mv | AT amandaqarawani mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT efratnaaman mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT ronybenzvielimelech mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT michalharel mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT shahafsigaldror mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT talibenzur mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT tamarziv mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT danieloffen mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies AT shirizayitsoudry mesenchymalstemcellderivedexosomesmitigateamyloidbinducedretinaltoxicityinsightsfromratmodelandcellularstudies |