Inhibiting NF-κB Signaling Activation Reduces Retinal Neovascularization by Promoting a Polarization Shift in
Ailing Sui1, Xiuping Chen1, Anna M Demetriades1
1,.
Investigative Ophthalmology & Visual Science
|June 4, 2020
Summary
Blocking Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling reduces retinal neovascularization (RNV) in mice. This occurs by shifting macrophage polarization from M1 to M2, decreasing inflammation and promoting healing.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling influences tumor angiogenesis and metastasis.
- The precise role of NF-κB in retinal neovascularization (RNV) is not fully understood.
Purpose of the Study:
- To investigate the role and mechanism of NF-κB in regulating RNV.
- To determine how NF-κB affects macrophage polarization in the context of RNV.
Main Methods:
- Utilized oxygen-induced retinopathy (OIR) mouse models.
- Assessed NF-κB signaling activation via immunofluorescence and western blotting.
- Quantified RNV and macrophage recruitment using retinal flat-mounts.
- Analyzed macrophage polarization and gene expression through flow cytometry, immunofluorescence, and RT-PCR.
Main Results:
- NF-κB signaling components (p-IκBα, p-p65) were upregulated in OIR mice.
- Inhibition of NF-κB with PDTC significantly decreased RNV.
- PDTC treatment led to decreased M1 macrophages and increased M2 macrophages, with corresponding changes in cytokine expression.
Conclusions:
- Inhibition of NF-κB signaling effectively reduces RNV in OIR mice.
- NF-κB blockade promotes the M1 to M2 macrophage polarization shift.
- This shift in macrophage polarization is a key mechanism by which NF-κB inhibition impacts RNV.
