Dysregulated DNA Methylation in Abca4-/- Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease

Stargardt disease (STGD1), the most common inherited juvenile macular degeneration, is caused by biallelic mutations in the <i>ABCA4</i> gene. Currently, there is no approved treatment. In this study, we investigated early-stage epigenomic changes in the retinal pigment epithelium (RPE) of <i>Abca4<sup>-/-</sup></i> mice, a well-established model of STGD1. Reduced representation bisulfite sequencing (RRBS) revealed hypermethylation of gene regions associated with disease-related pathways, implicating methyl-CpG-binding protein 2 (MeCP2) and RE1-silencing transcription factor (REST) as potential regulators. Notably, DNA methylation of a subset of genes preceded their transcriptional change and disease phenotypes in <i>Abca4<sup>-/-</sup></i> RPE. Together with the detected age-dependent increase in MeCP2 levels in <i>Abca4<sup>-/-</sup></i> RPE, these findings suggest that early DNA methylation changes may contribute to RPE dysfunction and eventual cell loss in STGD1.

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Publication Details

Journal
International Journal of Molecular Sciences
Published
2025-11-05
DOI
https://doi.org/10.3390/ijms262110742
Primary Topic
Retinal Development and Disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Dysregulated DNA Methylation in Abca4-/- Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease

Dorota Skowronska‐Krawczyk, Matteo Pellegrini, Arpita Dave, Marco Morselli et al.
International Journal of Molecular Sciences
Retinal Development and Disorders
article

Dysregulated DNA Methylation in Abca4-/- Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease

Dorota Skowronska‐Krawczyk, Matteo Pellegrini, Arpita Dave, Marco Morselli, Emily Tom, Anela Tosevska, Roxana A. Radu
article en

Abstract

Stargardt disease (STGD1), the most common inherited juvenile macular degeneration, is caused by biallelic mutations in the <i>ABCA4</i> gene. Currently, there is no approved treatment. In this study, we investigated early-stage epigenomic changes in the retinal pigment epithelium (RPE) of <i>Abca4<sup>-/-</sup></i> mice, a well-established model of STGD1. Reduced representation bisulfite sequencing (RRBS) revealed hypermethylation of gene regions associated with disease-related pathways, implicating methyl-CpG-binding protein 2 (MeCP2) and RE1-silencing transcription factor (REST) as potential regulators. Notably, DNA methylation of a subset of genes preceded their transcriptional change and disease phenotypes in <i>Abca4<sup>-/-</sup></i> RPE. Together with the detected age-dependent increase in MeCP2 levels in <i>Abca4<sup>-/-</sup></i> RPE, these findings suggest that early DNA methylation changes may contribute to RPE dysfunction and eventual cell loss in STGD1.

International Journal of Molecular SciencesVol. 26(21)
University of California, Los Angeles (US), Doheny Eye Institute (US), Medical University of Vienna (AT)
Research to Prevent Blindness, University of California, Irvine, David Geffen School of Medicine, University of California, Los Angeles
Openalex Percentile: Top 71%
Retinal Development and Disorders
DOIOpen Access PDFOpenAlex
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