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

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 (...

Full description

Bibliographic Details
Main 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
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/16/2/236
_version_ 1797297222476365824
author 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
author_facet 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
author_sort Xin Chen
collection DOAJ
description 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.
first_indexed 2024-03-07T22:18:10Z
format Article
id doaj.art-ad818e3812ca4ed39de3fc488946258a
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-03-07T22:18:10Z
publishDate 2024-02-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-ad818e3812ca4ed39de3fc488946258a2024-02-23T15:31:11ZengMDPI AGPharmaceutics1999-49232024-02-0116223610.3390/pharmaceutics16020236Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye DiseaseXin Chen0Na Lin1Jin-Miao Li2Haixia Liu3Anmar Abu-Romman4Ebru Yaman5Fang Bian6Cintia S. de Paiva7Stephen C. Pflugfelder8De-Quan Li9Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAAllergan, an AbbVie Company, Irvine, CA 92612, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAOcular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USAEctoine, 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.https://www.mdpi.com/1999-4923/16/2/236corneadry eyeectoineinflammationmurine model
spellingShingle 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
Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
Pharmaceutics
cornea
dry eye
ectoine
inflammation
murine model
title Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
title_full Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
title_fullStr Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
title_full_unstemmed Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
title_short Ectoine, from a Natural Bacteria Protectant to a New Treatment of Dry Eye Disease
title_sort ectoine from a natural bacteria protectant to a new treatment of dry eye disease
topic cornea
dry eye
ectoine
inflammation
murine model
url https://www.mdpi.com/1999-4923/16/2/236
work_keys_str_mv AT xinchen ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT nalin ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT jinmiaoli ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT haixialiu ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT anmaraburomman ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT ebruyaman ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT fangbian ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT cintiasdepaiva ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT stephencpflugfelder ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease
AT dequanli ectoinefromanaturalbacteriaprotectanttoanewtreatmentofdryeyedisease