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Updated: Oct 25, 2026
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Macrophage-Associated Profibrotic Programs in Diabetic Epiretinal Membrane and Their Modulation by Faricimab
Soo Young Lee1, Do Eon Kim1, Ahreum Kim1
1Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Purpose:
Epiretinal membrane (ERM) formation in diabetic retinal disease is frequently associated with inflammation and fibrosis; however, the underlying cellular mechanisms remain incompletely defined. We investigated whether macrophage-associated profibrotic programs contribute to diabetic ERM formation and whether these pathways are modulated by faricimab, a dual angiopoietin-2 (Ang2) and vascular endothelial growth factor A (VEGFA) inhibitor.
Methods:
Human ERM specimens obtained during vitrectomy were analyzed by immunohistochemistry to assess macrophage infiltration, including Tie2-expressing subsets. Macrophage-associated inflammatory and profibrotic responses were evaluated using PMA-stimulated THP-1-derived macrophages treated with faricimab, followed by quantitative real-time PCR analysis of inflammatory, profibrotic, and extracellular matrix-related genes. Publicly available transcriptomic datasets from human fibrovascular membranes were analyzed to examine coordinated activation of fibrosis-related gene programs.
Results:
ERMs from patients with diabetic retinopathy (DR) demonstrated increased macrophage infiltration and enrichment of Tie2-expressing macrophages compared with non-diabetic ERMs. In vitro, PMA-induced macrophage differentiation markedly upregulated inflammatory and profibrotic mediators, including TGF-β1, IL-10, IL-1RN, and CD163. Faricimab attenuated the expression of these genes in a concentration-dependent manner, with particularly prominent suppression of TGF-β1. Faricimab also reduced the expression of profibrotic and extracellular matrix-related genes, including ACTA2, fibronectin, MMP2, and MMP9. Transcriptomic analyses revealed coordinated upregulation of fibrosis-related gene networks and increased ACTA2 expression in fibrovascular membranes.
Conclusions:
Macrophage-associated profibrotic programs are associated with ERM formation in diabetic retinal diseases. Faricimab modulates macrophage polarization and fibrotic gene expression, providing a potential biological context for the observed antifibrotic effects of dual Ang2 and VEGFA inhibition.
