PM Dysregulates Epithelial Barrier Function in Human Corneal Epithelial Cells That is Restored by Antioxidant SKQ1

Overview

Journal Toxicol Appl Pharmacol

Specialties Pharmacology
Toxicology

Date 2024 Oct 11

PMID 39393465

Authors

Mallika Somayajulu

Robert Wright

Farooq Muhammed

Sharon A McClellan

Ahmed Ibrahim

Linda D Hazlett

Affiliations

Soon will be listed here.

Abstract

Exposure to airborne particulate <10 μm (PM) adversely affects the ocular surface. This study tested PM on epithelial barrier integrity in immortalized human corneal epithelial cells (HCE-2) and mouse cornea, and whether antioxidant SKQ1 is restorative. HCE-2 were exposed to 100 μg/ml PM ± SKQ1 for 24 h. An Electric Cell-Substrate Impedance Sensing (ECIS) system monitored the impact of PM. RT-PCR, western blotting and immunofluorescence measured levels of barrier and associated proteins, stanniocalcin 2 (STC2), and a kit measured total calcium. In vivo, female C57BL/6 mice were exposed to either control air or PM (±SKQ1) in a whole-body exposure chamber, and barrier associated proteins tested. Tight junction and mucins proteins in the cornea were tested. In HCE-2, PM vs control significantly reduced mRNA and protein levels of tight junction and adherence proteins, and mucins. ECIS data demonstrated that PM vs control cells exhibited a significant decrease in epithelial barrier strength at 4000 Hz indicated by reduced impedance and resistance. PM also upregulated STC2 protein and total calcium levels. In vivo, PM vs control reduced zonula occludens 1 and mucins. SKQ1 pre-treatment reversed PM effects both in vitro and in vivo. In conclusion, PM exposure reduced tight junction and mucin proteins, and compromised the seal between cells in the corneal epithelium leading to decreased epithelial barrier strength. This effect was reversed by SKQ1. Since the corneal epithelium forms the first line of defense against air pollutants, including PM, preserving its integrity using antioxidants such as SKQ1 is crucial in reducing the occurrence of ocular surface disorders.

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