Disulfiram Ophthalmic Solution Inhibited Macrophage Infiltration by Suppressing Macrophage Pseudopodia Formation in a Rat Corneal Alkali Burn Model

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.

A Novel Multi-Observation System to Study the Effects of Anterior Ocular Inflammation in Zinn’s Zonule Using One Specimen

“…Although there are reports of macroscopic observation with gelatin embedding [ 10 ], it was necessary to use a separate specimen for each of those microscopic morphological changes and cellular observations. In addition, IHC with LV-SEM has been used in the renal region [ 11 , 12 , 13 ], but there are few reports of its use for observation of the eye [ 14 , 15 ]. In this study, we succeeded in preparing paraffin-substitutable specimens from gelatin-embedded specimens by using low-melting-point gelatin.…”

PharmGKB summary: disulfiram pathway

“…The mechanism by which disulfiram triggers these aversive physical reactions is, at least in part, somewhat understood. However, new studies suggest novel pharmacodynamic roles for disulfiram; including the treatment of opioid use disorder and therapy resistance [20], preventing sepsis and tumor growth [5], and in regulating macrophage-elicited immune response [21].…”

Molecular and Cellular Mechanisms of Corneal Scarring and Advances in Therapy

“…Disulfiram (DSF), a drug treatment for alcoholism, has been found to have FROUNT (a macrophage stimulator) inhibitory activity. Ikebukuro et al showed that DSF eye drops reduced macrophage accumulation in a rat corneal alkali burn model [17].…”