Single-Cell Multiomics Profiling Reveals Heterogeneity of Müller Cells in the Oxygen-Induced Retinopathy Model

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Retinal neovascularization is a significant cause of vision loss and blindness.
• The precise molecular mechanisms driving retinal neovascularization remain incompletely understood.
• Proliferative diabetic retinopathy (PDR) is a severe complication characterized by abnormal blood vessel growth in the retina.

Purpose of the Study:

• To comprehensively investigate the molecular mechanisms of retinal neovascularization using single-cell multiomics.
• To identify key cell types and molecular pathways involved in oxygen-induced retinopathy (OIR).
• To explore the association between ocular cell types and PDR using integrated multiomics and GWAS data.

Main Methods:

• Induction of OIR in mice followed by single-nucleus isolation and multiomics sequencing.
• Integration of single-cell data with genome-wide association study (GWAS) data.
• Cell communication analysis, trajectory analysis of Müller cells, and pathway analysis with human retinal data.

Main Results:

• Six major ocular cell classes were identified, with Müller cells/astrocytes significantly associated with PDR.
• Key cell communication pathways (e.g., Vegfa-Vegfr2, Igf1-Igf1r) linked to vascular proliferation and neurodevelopment were highlighted.
• A subset of Müller cells expressing photoreceptor degeneration genes was identified, and OIR Müller cells/astrocytes showed altered gene expression related to axon development and neurotransmitter transmission.

Conclusions:

• Müller cells play a critical role in the pathogenesis of retinal neovascularization.
• The study elucidates cellular and molecular pathways implicated in retinal neovascularization and PDR.
• Identified pathways represent potential therapeutic targets for PDR, guiding future research and clinical interventions.