Language

English

Publication Date

12-1-2025

Journal

Experimental Eye Research

DOI

10.1016/j.exer.2025.110677

PMID

41038369

PMCID

PMC13133920

PubMedCentral® Posted Date

5-2-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

In the studies of Inherited Retinal Diseases (IRDs), the knockout of traditional animal models like mice often fails to accurately replicate human phenotypes due to genetic and anatomical differences. Human retinal organoids (ROs) derived from stem cells have emerged as promising developmental models in retinal studies to delineate cell growth, but their ability to represent the characteristics of late-onset IRDs remains unclear. This study aims to validate ROs as a disease model for Stargardt's Disease (STGD) caused by ABCA4 mutations. Using single-cell RNA sequencing, ROs from 2 STGD patients were compared with healthy control-derived ROs at two developmental stages on both the cellular and transcriptomic levels. The results from gene-level comparisons show promising evidence that ROs successfully capture the underlying molecular variations between patient and control samples even at the early developmental stage, providing the potential of applying ROs to facilitate the study of IRDs and late-onset neurodegenerative diseases.

Keywords

Humans, Organoids, Mutation, ATP-Binding Cassette Transporters, Retina, Stargardt Disease, Male, Female, Retinal Diseases, ABCA4, Inherited retinal diseases (IRDs), Stargardt’s Disease (STGD), Retinal organoids (ROs), Single-cell RNA sequencing (scRNA-seq)

Published Open-Access

yes

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