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Lookup NU author(s): Dr Joseph Collin, Dr Megan Hasoon, Zerti Zerti, Sarah Hammadi, Professor David SteelORCiD, Raf Hussain, Dr Jonathan Coxhead, Dr Steven LisgoORCiD, Dr Rachel Queen, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2023. Published by Oxford University Press.Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the developed world. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlying retinal pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression to intermediate and advanced stages AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) of human fetal and adult RPE-choroidal tissues, profiling in detail all the cell types and elucidating cell type-specific proliferation, differentiation and immunomodulation events that occur up to midgestation. Our data demonstrate that progression from the fetal to adult state is characterized by an increase in expression of genes involved in the oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE-choroid tissue. Single-cell comparative transcriptional analysis between a patient with intermediate AMD and an unaffected subject revealed a reduction in the number of RPE cells and melanocytes in the macular region of the AMD patient. Together these findings may suggest a macular loss of RPE cells and melanocytes in the AMD patients, but given the complex processing of tissues required for single-cell RNA-Seq that is prone to technical artefacts, these findings need to be validated by additional techniques in a larger number of AMD patients and controls.
Author(s): Collin J, Hasoon MSR, Zerti D, Hammadi S, Dorgau B, Clarke L, Steel D, Hussain R, Coxhead J, Lisgo S, Queen R, Lako M
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2023
Volume: 32
Issue: 10
Pages: 1698-1710
Print publication date: 15/05/2023
Online publication date: 16/01/2023
Acceptance date: 12/01/2023
Date deposited: 22/05/2023
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: https://doi.org/10.1093/hmg/ddad007
DOI: 10.1093/hmg/ddad007
PubMed id: 36645183
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