Macrophage-Associated Profibrotic Programs in Diabetic Epiretinal Membrane and Their Modulation by Faricimab
Year: 2026
Type: article
Abstract: 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.
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,850
OpenAlex ID: W7223182158