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Single-cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration

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.

Publication metadata

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


DOI: 10.1093/hmg/ddad007

PubMed id: 36645183


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Funder referenceFunder name
MR/R006237/1Medical Research Council (MRC)
MR/S035826/1Medical Research Council (MRC)