Skip to content
DraconiticResearch
Search Sources API
203,948 studies31 sourcesUpdated 45 min ago
Peer-reviewedCC BY-NC-ND 4.0Investigative Ophthalmology & Visual Science

Macrophage-Associated Profibrotic Programs in Diabetic Epiretinal Membrane and Their Modulation by Faricimab

  • Soo Young Lee1
  • Do Eon Kim1
  • Ahreum Kim1
  • Hyunmi Kim1
  • Soo Jin Kim1
  • Junyeop Lee1,2
  1. 1Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  2. 2Graduate School of Health Science and Technology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
Read full textDOICite

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.

Related

  1. Fucosyltransferase 8 is associated with post-thrombotic vein wall fibrosis and macrophage profibrotic signaling.
    Guodong Du, Yu Jin, Hongji Pu +4
    JVS-vascular sciencePeer-reviewedCC BY-NC-NDFull textSurgery & anaesthesiaEurope PMCPMC
  2. Variables Associated With Faricimab Treatment Durability in Neovascular Age-Related Macular Degeneration : A Post Hoc Analysis of the TENAYA and LUCERNE Trials
    Colin S. Tan, Benjamin Bakall, Adrian Hock Chuan Koh +8
    JAMA ophthalmologyPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  3. Early Macular Leakage Resolution Is Associated with Extended Faricimab Dosing in Retinal Vein Occlusion: A BALATON/COMINO Post Hoc Analysis
    Christiana Dinah, Harit K. Bhatt, Hemal Mehta +7
    Ophthalmology and TherapyPeer-reviewedCC BY-NCFull textGeneral medicineDOAJ
  4. Nanotherapeutic macrophage reprogramming through immunometabolic and microbial modulation for sepsis treatment.
    Xintong Lu, Wenhui Wang, Bingjie Zhang +11
    Signal transduction and targeted therapyPeer-reviewedCC BY-NC-NDFull textGeneral biologyGeneral medicineEurope PMCDOAJ
  5. Immunometabolic Modulation by Low‐Dose Sodium Butyrate: PI3K/Akt/mTOR Signalling Orchestrates Macrophage Polarization to Protect Against Clostridioides difficile Colitis
    Sisi Zhang, Zhou Jingxiang, Caixia Tan +5
    ImmunologyPeer-reviewedCC BY 4.0Full textInfectious diseasePMC

Cite

BibTeXRIS
BibTeX
@article{lee2026macrophageassociated,
  title = {{Macrophage-Associated Profibrotic Programs in Diabetic Epiretinal Membrane and Their Modulation by Faricimab}},
  author = {Soo Young Lee and Do Eon Kim and Ahreum Kim and Hyunmi Kim and Soo Jin Kim and Junyeop Lee},
  journal = {Investigative Ophthalmology \& Visual Science},
  year = {2026},
  month = oct,
  doi = {10.1167/iovs.67.12.51},
  url = {https://doi.org/10.1167/iovs.67.12.51},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Macrophage-Associated Profibrotic Programs in Diabetic Epiretinal Membrane and Their Modulation by Faricimab
AU  - Soo Young Lee
AU  - Do Eon Kim
AU  - Ahreum Kim
AU  - Hyunmi Kim
AU  - Soo Jin Kim
AU  - Junyeop Lee
PY  - 2026
DA  - 2026/10/22
JO  - Investigative Ophthalmology & Visual Science
DO  - 10.1167/iovs.67.12.51
UR  - https://doi.org/10.1167/iovs.67.12.51
AB  - 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.
SN  - 0146-0404
SN  - 1552-5783
ER  -