Supplementary information files for Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina

Supplementary files for article Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithe...

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Main Authors: Marzena Kurzawa-Akanbi, Phillip Whitfield, Florence Burté, Pietro Maria Bertelli, Varun Pathak, Mary Doherty, Birthe Hilgen, Lina Gliaudelyte, Mark Platt, Rachel Queen, Jonathan Coxhead, Andrew Porter, Maria Öberg, Daniela Fabrikova, Tracey Davey, Chia Shyan Beh, Maria Georgiou, Joseph Collin, Veronika Boczonadi, Anetta Härtlova, Michael Taggart, Jumana Al-Aama, Viktor I Korolchuk, Christopher M Morris, Jasenka Guduric-Fuchs, David H Steel, Reinhold J Medina, Lyle Armstrong, Majlinda Lako
Format: Data Data
Published: 2023
Subjects:
Biochemistry and cell biology
Age-related macular degeneration
Complement factor H
extracellular vesicles
Human induced pluripotent stem cells
Retinal pigment epithelium
Photoreceptors
Retina
Online Access:https://dx.doi.org/10.17028/rd.lboro.22692214.v1
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Summary:Supplementary files for article Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient-specific RPE cells with the Complement Factor H Y402H high-risk polymorphism to perform a comprehensive analysis of extracellular vesicles (EVs), their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced polarised EV secretion. Multi-omics analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids, which mediate key AMD features including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. Moreover, AMD RPE EVs induce amyloid fibril formation, revealing their role in drusen formation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the acquisition of AMD features such as stress vacuoles, cytoskeletal destabilization and abnormalities in the morphology of the nucleus. Retinal organoid treatment with apical AMD RPE EVs leads to disrupted neuroepithelium and the appearance of cytoprotective alpha B crystallin immunopositive cells, with some co-expressing retinal progenitor cell markers Pax6/Vsx2, suggesting injury-induced regenerative pathways activation. These findings indicate that AMD RPE EVs are potent inducers of AMD phenotype in the neighbouring RPE and retinal cells. 

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