Inhibition of Monocyte Chemoattractant Protein 1 Prevents Conjunctival Fibrosis in an Experimental Model of Glaucoma Filtration Surgery.
Chong Rachel Shujuan, Lee Ying Shi, Chu Stephanie Wai Ling, Toh Li Zhen, Wong Tina Tzee Ling
AI Summary
MCP-1 inhibition in mice prevented conjunctival fibrosis after glaucoma surgery, showing superior bleb survival and less cellular toxicity than MMC. This suggests a safer antifibrotic alternative for patients.
Abstract
Purpose
To evaluate the effect of treatment with monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) to maintain bleb survival and prevent fibrosis in an experimental model of glaucoma filtration surgery (GFS).
Methods
GFS was performed on one eye of C57/Bl6 mice (n = 36) that was treated with MCP-Ri, mitomycin-C (MMC), or vehicle at the time of surgery. Real-time polymerase chain reaction was used to evaluate conjunctival expression of monocyte chemoattractant protein-1 (MCP-1), TGFB1, TGFB2, collagen 1a1 (Col1a1), sparc (Sparc), and fibronectin at 2 and 7 days following surgery. Anterior segment slit-lamp examination, optical coherence tomography, and confocal microscopy were performed in vivo at day 14. Eyes were processed for immunohistochemical staining of F4/80, a monocyte-macrophage marker, at day 2. In vitro experiments were also performed to compare the effect of MMC, MCP-Ri, and vehicle on the viability of mouse Tenon's fibroblasts.
Results
Treatment with MCP-Ri results in a greater reduction in the percentage of F4/80-positive cells in conjunctival blebs and lesser MCP-1 gene expression following experimental GFS than MMC or control. Both MMC and MCP-Ri reduced Col1a1 and Sparc expression, but not fibronectin. TGFB1 decreased with MCP-Ri but not MMC; MMC but not MCP-Ri reduced TGFB2. MMC and MCP-Ri treatment resulted in the preservation of bleb height at day 14, as compared to control. MCP-Ri was less toxic to mouse Tenon's fibroblasts in comparison with MMC.
Conclusions
Targeting MCP-1 results in prolonged bleb survival following experimental GFS with less cellular toxicity as compared to MMC. MCP inhibition could provide a safer alternative to conventional antifibrotic adjunctive treatments in GFS.
MeSH Terms
Shields Classification
Key Concepts6
Treatment with monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) resulted in a greater reduction in the percentage of F4/80-positive cells in conjunctival blebs and lesser MCP-1 gene expression following experimental glaucoma filtration surgery (GFS) in C57/Bl6 mice (n=36) compared to mitomycin-C (MMC) or control.
Both mitomycin-C (MMC) and monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) reduced collagen 1a1 (Col1a1) and sparc (Sparc) expression, but not fibronectin, following experimental glaucoma filtration surgery (GFS) in C57/Bl6 mice (n=36).
TGFB1 expression decreased with monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) but not mitomycin-C (MMC), while MMC but not MCP-Ri reduced TGFB2 expression following experimental glaucoma filtration surgery (GFS) in C57/Bl6 mice (n=36).
Treatment with mitomycin-C (MMC) and monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) resulted in the preservation of bleb height at day 14 following experimental glaucoma filtration surgery (GFS) in C57/Bl6 mice (n=36), as compared to control.
Monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) was less toxic to mouse Tenon's fibroblasts in vitro compared to mitomycin-C (MMC).
Targeting monocyte chemoattractant protein-1 (MCP-1) with MCP-Ri could provide a safer alternative to conventional antifibrotic adjunctive treatments in glaucoma filtration surgery (GFS), due to prolonged bleb survival with less cellular toxicity compared to mitomycin-C (MMC) in an experimental model of GFS in C57/Bl6 mice (n=36).
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