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Updated: Aug 15, 2025
Author Spotlight: Decoding Corneal Neovascularization with Alkali Burn Model for Future Therapeutic Strategies
Published on: June 30, 2023
Disulfiram Ophthalmic Solution Inhibited Macrophage Infiltration by Suppressing Macrophage Pseudopodia Formation in a
Toyo Ikebukuro1,2, Takeshi Arima1,2, Momoko Kasamatsu1,2
1Department of Ophthalmology, Nippon Medical School, Tokyo 113-8603, Japan.
Abstract:
FROUNT is an intracellular protein that promotes pseudopodia formation by binding to the chemokine receptors CCR2 and CCR5 on macrophages. Recently, disulfiram (DSF), a drug treatment for alcoholism, was found to have FROUNT inhibitory activity. In this study, we investigated the effect of DSF eye drops in a rat corneal alkali burn model. After alkali burn, 0.5% DSF eye drops (DSF group) and vehicle eye drops (Vehicle group) were administered twice daily. Immunohistochemical observations and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at 6 h and 1, 4, and 7 days after alkali burn. Results showed a significant decrease in macrophage accumulation in the cornea in the DSF group, but no difference in neutrophils. RT-PCR showed decreased expression of macrophage-associated cytokines in the DSF group. Corneal scarring and neovascularization were also suppressed in the DSF group. Low-vacuum scanning electron microscopy imaging showed that macrophage length was significantly shorter in the DSF group, reflecting the reduced extension of pseudopodia. These results suggest that DSF inhibited macrophage infiltration by suppressing macrophage pseudopodia formation.
Insights
Disulfiram (DSF) eye drops reduced macrophage infiltration and corneal scarring in a rat alkali burn model. DSF suppressed macrophage pseudopodia formation, a key step in their infiltration.
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- FROUNT protein regulates macrophage pseudopodia formation via chemokine receptors CCR2 and CCR5.
- Disulfiram (DSF), an alcoholism treatment, inhibits FROUNT activity.
- Corneal alkali burns trigger inflammatory responses involving macrophages.
Purpose of the Study:
- To investigate the therapeutic potential of disulfiram (DSF) eye drops in a rat corneal alkali burn model.
- To determine DSF's effect on macrophage infiltration and pseudopodia formation in corneal injury.
Main Methods:
- A rat corneal alkali burn model was established.
- 0.5% DSF or vehicle eye drops were administered twice daily post-injury.
- Immunohistochemistry, RT-PCR, and scanning electron microscopy were used for analysis at various time points.
Main Results:
- DSF treatment significantly decreased macrophage accumulation and expression of macrophage-associated cytokines in the cornea.
- Neutrophil infiltration remained unchanged.
- Corneal scarring and neovascularization were suppressed in the DSF group.
- Macrophage length, indicative of pseudopodia extension, was significantly reduced by DSF.
Conclusions:
- DSF eye drops effectively inhibit macrophage infiltration in corneal alkali burns by suppressing pseudopodia formation.
- DSF demonstrates potential as a therapeutic agent for managing corneal inflammatory conditions and promoting healing.
