Mesenchymal drift in ciliopathy iPSC-derived RPE reveals a convergent pathogenic cell state.

Ciliopathy iPSC-derived RPE uniformly exhibit mesenchymal drift driven by TGF-β signaling, revealing a common pathogenic cell state across diverse genetic mutations.

• Why it matters: Understanding shared pathways in ciliopathies is crucial because current gene-specific therapies are costly and limited in scope, hindering broad treatment options for retinal degeneration.
• What they did: Researchers developed iPSC-derived RPE models from nine ciliopathy patients with different genetic mutations and observed consistent epithelial polarization defects and mitochondrial impairment linked to TGF-β dysregulation.
• The result: The study identified pioglitazone and galunisertib as promising drugs to target these common pathogenic features, paving the way for mutation-agnostic therapies for ciliopathy-related retinal degeneration.