Feasibility analysis of Sinomenine alleviating fibrosis of filtering bleb after glaucoma filtering surgery: a mini review

Abstract

Fibrosis of the filtering bleb remains the predominant cause of glaucoma filtering surgery failure, mediated by interconnected pathological processes including postoperative local inflammation, aberrant fibroblast proliferation, and deposition of the extracellular matrix (ECM). The antimetabolite drugs 5-fluorouracil (5-FU) and mitomycin C (MMC) are effective in preventing filtering bleb fibrosis, but their non-specific cytotoxic effects necessitate the development of targeted therapeutic alternatives. Fibrosis is a group of diseases with similar pathological mechanisms and molecular features. By analyzing evidence of Sinomenine's (SIN) anti-fibrotic effects across multiple organs, this study explores its potential use in glaucoma filtration surgery (GFS) to reduce scarring: (1) SIN inhibits trauma-induced NF-κB activation in Tenon's fibroblasts (TFs), reduces neutrophil and macrophage infiltration, and suppresses cytokine cascades. Besides, SIN targets the phosphatidylinositol-3-kinase (PI3K)/Akt pathway to attenuate macrophage M2 polarization and neutrophil recruitment, thereby interrupting fibrotic progression. (2) SIN suppresses transforming growth factor-β (TGF-β)/Smad3 signaling and inhibits the transdifferentiation of fibroblasts into α smooth muscle actin (α SMA) expressing myofibroblasts (MFs). SIN also blocks fibroblast proliferation and migration via PI3K/Akt/mTORC1 axis inhibition, restraining myofibroblast differentiation-the central pathological event in filtering bleb scarring. SIN shows antifibrotic efficacy, and feasibility studies on its application may offer novel insights into antifibrotic strategies.

Keywords: Sinomenine; fibrosis; filtering bleb; glaucoma; glaucoma filtering surgery.

Figure 1

Stages of wound healing following glaucoma filtration surgery. (Fibrosis of filtering blebs following GFS is predominantly mediated by the proliferation, migration, and contractile activity of TFs. Surgical trauma triggers vascular disruption, releasing platelets and blood components that initiate coagulation cascades. Necrotic tissue debris, coagulative processes, and microbial infiltration collectively induce inflammatory activation. Inflammatory cells infiltrate the wound site to phagocytize cellular debris and pathogens while secreting growth factors and cytokines, including TGF-β, VEGF, PDGF, and IL-6. During the proliferative phase, neovascularization occurs while TFs are activated and transdifferentiate into MFs expressing α-SMA. Concurrently, ECM synthesis establishes a granulation tissue scaffold, facilitating wound contraction and repair. Ultimately, ECM remodeling occurs, culminating in the maturation of granulation tissue into dense fibrotic scar tissue).