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Microglial Phagocytosis of Bipolar Cells Triggers Inner Retinal Degeneration in Rs1-KO Mice

GSE303947 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/02/25 Platform GPL24247
Summary
X-linked retinoschisis (XLRS), caused by Retinoschisin 1 (RS1) gene mutations, leads to progressive retinal degeneration. While photoreceptor loss is a hallmark of the disease, its early pathogenic mechanisms are not well understood. Using CRISPR/Cas9-edited Rs1-exon2-knockout mice, we investigated the temporal progression of the retinal degeneration. Single-cell RNA sequencing revealed that the degeneration of bipolar cells, particularly the OFF-cone subtype, precedes photoreceptor loss. This early degeneration was driven by microglial activation and their subsequent phagocytosis of bipolar cells via phosphatidylserine exposure and C3b activation that was independent of apoptosis. These findings reveal a temporal sequence of neurodegeneration in XLRS, highlighting bipolar cells as a critical therapeutic target for early intervention.
Published in
Microglial phagocytosis of bipolar cells triggers inner retinal degeneration in Rs1-KO mice
Yang JY, Chang HS, Kim YJ et al. · Cell communication and signaling : CCS 2026 · PMID 41593663 · doi:10.1186/s12964-026-02692-8
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Also filed as BioProject PRJNA1298285 and SRA study SRP604333. Searching any of these in the dataset finder brings you back here.

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