Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease

Authors

Xin Chen
Na Lin
Jin-Miao Li
Haixia Liu
Anmar Abu-Romman
Ebru Yaman
Fang Bian
Cintia S de Paiva
Stephen C Pflugfelder
De-Quan Li

Publication Date

2-5-2024

Journal

Pharmaceutics

DOI

10.3390/pharmaceutics16020236

PMID

38399289

PMCID

PMC10892505

PubMedCentral® Posted Date

2-5-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

cornea, dry eye, ectoine, inflammation, murine model

Abstract

Ectoine, a novel natural osmoprotectant, protects bacteria living in extreme environments. This study aimed to explore the therapeutic effect of ectoine for dry eye disease. An experimental dry eye model was created in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls (UT). DS mice were dosed topically with 0.5-2.0% of ectoine or a vehicle control. Corneal epithelial defects were detected via corneal smoothness and Oregon Green dextran (OGD) fluorescent staining. Pro-inflammatory cytokines and chemokines were evaluated using RT-qPCR and immunofluorescent staining. Compared with UT mice, corneal epithelial defects were observed as corneal smoothness irregularities and strong punctate OGD fluorescent staining in DS mice with vehicle. Ectoine treatment protected DS mice from corneal damage in a concentration-dependent manner, and ectoine at 1.0 and 2.0% significantly restored the corneal smoothness and reduced OGD staining to near normal levels. Expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines CCL3 and CXCL11 was significantly elevated in the corneas and conjunctivas of DS mice, whereas 1.0 and 2.0% ectoine suppressed these inflammatory mediators to near normal levels. Our findings demonstrate that ectoine can significantly reduce the hallmark pathologies associated with dry eye and may be a promising candidate for treating human disease.