Rebamipide Enhances Pathogen Defense and Mitigates Inflammation in a Particulate Matter-Induced Ocular Surface Inflammation Rat Model

TL;DR

This study shows that rebamipide eye drops reduce inflammation and improve eye health in rats exposed to particulate matter.

Contribution

The study demonstrates rebamipide's novel efficacy in mitigating PM-induced ocular inflammation compared to hyaluronic acid.

Findings

2% rebamipide reduced inflammatory markers like MMP-9, IL-1β, and TNF-α in PM-exposed rats.

Rebamipide enhanced mucin secretion and pathogen clearance via NF-κB and EGFR pathways.

Rebamipide improved goblet cell density and reduced apoptosis and uncontrolled cell proliferation.

Abstract

Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular surface inflammation model using Sprague–Dawley (SD) rats. Parameters including clinical signs, histological changes, mucin secretions, inflammatory cytokines, mast cell degranulation, dysregulated cell proliferation, and cellular apoptosis were evaluated. 2% REB alleviated ocular surface inflammation by downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and upregulating epidermal growth factor receptor (EGFR) signaling, thereby enhancing mucin secretion and promoting pathogen clearance. Histopathological analysis, western blot, and immunohistochemical staining revealed a marked reduction in inflammatory markers including MMP-9, IL-1β, TNF-α, IL-17, and CD-4, decreased mast cell degranulation, increased goblet cell density, and enhanced expression of mucins, including MUC5AC and MUC16, in the 2% REB-treated group compared to the 0.1% HA-treated and PM-exposed groups. Moreover, 2% REB demonstrated decreased apoptosis (TUNEL) and reduced uncontrolled cell proliferation (Ki67), indicating improved cellular integrity. In conclusion, 2% REB is a promising treatment option for PM-induced ocular surface inflammation in a rat model compared with 0.1% HA, offering the benefits of reducing inflammation, clearing pathogens, and protecting overall ocular health.

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