iPSC-derived RPE and retinal organoids from two phenotypically different Stargardt disease patients show differences in ABCA4 function
Abstract
Stargardt disease is a phenotypically heterogeneous disease caused by bi-allelic mutations in the ABCA4 gene. We generated retinal pigment epithelium (RPE) cells, photoreceptor precursors (PhRPs), and retinal organoids (ROs) from two induced pluripotent stem (iPS) cell lines derived from two phenotypically different Stargardt disease patients. We observed that RPE cells from the patient with peripheral affectation showed reduced ABCA4 expression, reduced phagocytosis and digestion of photoreceptor outer segments (POSs), and accumulation of lipid byproducts. ROs from both patients show stunted segments, more rods, caspase-3 activation, and lipofuscin accumulation at week 45 of maturation. Phenotypical differences seen in Stargardt disease patients are caused by their specific ABCA4 variants, but cellular and molecular mechanisms underlying the process of photoreceptor degeneration are still poorly understood. Here, we suggest that peripheral phenotypes associated with these macular dystrophies can be linked to poor clearance of POSs by RPE cells, giving these cells a higher role in the pathogenesis of the disease.
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BibTeX
@article{navinesferrer2026ipscderived,
title = {{iPSC-derived RPE and retinal organoids from two phenotypically different Stargardt disease patients show differences in ABCA4 function}},
author = {Arnau Navinés-Ferrer and Pilar Méndez-Vendrell and Laura Siles and Rafael Navarro and Anniken Burés-Jelstrup and Esther Pomares},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117998},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03381-X},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - iPSC-derived RPE and retinal organoids from two phenotypically different Stargardt disease patients show differences in ABCA4 function
AU - Arnau Navinés-Ferrer
AU - Pilar Méndez-Vendrell
AU - Laura Siles
AU - Rafael Navarro
AU - Anniken Burés-Jelstrup
AU - Esther Pomares
PY - 2026
DA - 2026/10/28
JO - iScience
DO - 10.1016/j.isci.2026.117998
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03381-X
AB - Stargardt disease is a phenotypically heterogeneous disease caused by bi-allelic mutations in the ABCA4 gene. We generated retinal pigment epithelium (RPE) cells, photoreceptor precursors (PhRPs), and retinal organoids (ROs) from two induced pluripotent stem (iPS) cell lines derived from two phenotypically different Stargardt disease patients. We observed that RPE cells from the patient with peripheral affectation showed reduced ABCA4 expression, reduced phagocytosis and digestion of photoreceptor outer segments (POSs), and accumulation of lipid byproducts. ROs from both patients show stunted segments, more rods, caspase-3 activation, and lipofuscin accumulation at week 45 of maturation. Phenotypical differences seen in Stargardt disease patients are caused by their specific ABCA4 variants, but cellular and molecular mechanisms underlying the process of photoreceptor degeneration are still poorly understood. Here, we suggest that peripheral phenotypes associated with these macular dystrophies can be linked to poor clearance of POSs by RPE cells, giving these cells a higher role in the pathogenesis of the disease.
SN - 2589-0042
ER -