scholarly journals Integrin αv and Vitronectin Prime Macrophage-Related Inflammation and Contribute the Development of Dry Eye Disease

2021 ◽  
Vol 22 (16) ◽  
pp. 8410
Author(s):  
Tsung-Chuan Ho ◽  
Shu-I Yeh ◽  
Show-Li Chen ◽  
Yeou-Ping Tsao
Keyword(s):  
Dry Eye ◽  
Macrophage Activation ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Inflammatory Gene Expression ◽  
Murine Bone Marrow ◽  
Culture Model ◽  
Inflammatory Processes ◽  
Corneal Damage

Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.

scholarly journals Lipid Annotation by Combination of UHPLC-HRMS (MS), Molecular Networking, and Retention Time Prediction: Application to a Lipidomic Study of In Vitro Models of Dry Eye Disease

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 225 ◽  
Author(s):  
Romain Magny ◽  
Anne Regazzetti ◽  
Karima Kessal ◽  
Gregory Genta-Jouve ◽  
Christophe Baudouin ◽  
...  
Keyword(s):  
Dry Eye ◽  
Retention Time ◽  
Inflammatory Responses ◽  
In Vitro Models ◽  
Dry Eye Disease ◽  
Molecular Networks ◽  
Chromatographic Behavior ◽  
Eye Disease ◽  
Molecular Networking

Annotation of lipids in untargeted lipidomic analysis remains challenging and a systematic approach needs to be developed to organize important datasets with the help of bioinformatic tools. For this purpose, we combined tandem mass spectrometry-based molecular networking with retention time (tR) prediction to annotate phospholipid and sphingolipid species. Sixty-five standard compounds were used to establish the fragmentation rules of each lipid class studied and to define the parameters governing their chromatographic behavior. Molecular networks (MNs) were generated through the GNPS platform using a lipid standards mixture and applied to lipidomic study of an in vitro model of dry eye disease, i.e., human corneal epithelial (HCE) cells exposed to hyperosmolarity (HO). These MNs led to the annotation of more than 150 unique phospholipid and sphingolipid species in the HCE cells. This annotation was reinforced by comparing theoretical to experimental tR values. This lipidomic study highlighted changes in 54 lipids following HO exposure of corneal cells, some of them being involved in inflammatory responses. The MN approach coupled to tR prediction thus appears as a suitable and robust tool for the discovery of lipids involved in relevant biological processes.

scholarly journals Manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin, a superoxide dismutase mimetic, reduces disease severity in in vitro and in vivo models for dry-eye disease

2019 ◽  
Vol 17 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Agnė Žiniauskaitė ◽  
Symantas Ragauskas ◽  
Anita K. Ghosh ◽  
Rubina Thapa ◽  
Anne E. Roessler ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Disease Severity ◽  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
In Vivo Models

scholarly journals Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1

2018 ◽  
Vol 9 ◽  
Author(s):  
Karima Kessal ◽  
Hong Liang ◽  
Ghislaine Rabut ◽  
Philippe Daull ◽  
Jean-Sébastien Garrigue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Dry Eye ◽  
Expression Profiling ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals GlicoPro, Novel Standardized and Sterile Snail Mucus Extract for Multi-Modulative Ocular Formulations. New Perspective in Dry Eye Disease Management

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2139
Author(s):  
Rita Mencucci ◽  
Giovanni Strazzabosco ◽  
Virginia Cristofori ◽  
Andrea Alogna ◽  
Daria Bortolotti ◽  
...  
Keyword(s):  
Dry Eye ◽  
Sodium Hyaluronate ◽  
Ophthalmic Solution ◽  
Dry Eye Disease ◽  
Mass Spectrometry Analysis ◽  
Corneal Epithelial Cell ◽  
Eye Disease ◽  
Corneal Cells ◽  
Anti Inflammatory

This study aimed to evaluate the mucoadhesive and regenerative properties of a novel lubricating multimolecular ophthalmic solution (GlicoPro®) extracted from snail mucus and its potential anti-inflammatory and analgesic role in the management of dry eye disease (DED). GlicoPro bio-adhesive efficacy was assessed using a lectin-based assay, and its regenerative properties were studied in a human corneal epithelial cell line. In vitro DED was induced in human corneal tissues; the histology and mRNA expression of selected genes of inflammatory and corneal damage biomarkers were analyzed in DED tissues treated with GlicoPro. A higher percentage of bio-adhesivity was observed in corneal cells treated with GlicoPro than with sodium hyaluronate-based compounds. In the scratch test GlicoPro improved in vitro corneal wound healing. Histo-morphological analysis revealed restoration of cellular organization of the corneal epithelium, microvilli, and mucin network in DED corneal tissues treated with GlicoPro. A significant reduction in inflammatory and ocular damage biomarkers was observed. High-performance liquid chromatography-mass spectrometry analysis identified an endogenous opioid, opiorphin, in the peptide fraction of GlicoPro. In conclusion, GlicoPro induced regeneration and bio-adhesivity in corneal cells; moreover, considering its anti-inflammatory and analgesic properties, this novel ophthalmic lubricating solution may be an innovative approach for the management of DED.

scholarly journals The effect of Polydatin in dry eye disease in vivo and in vitro

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Bongkyun Park ◽  
Tae Gu Lee ◽  
Soo‐Wang Hyun ◽  
Kyuhyung Jo ◽  
Ik Soo Lee ◽  
...  
Keyword(s):  
Dry Eye ◽  
Dry Eye Disease ◽  
Eye Disease

scholarly journals Antioxidant Effects of the Prenylated Flavonoid, Xanthohumol, on Corneal Epithelial Cells in Experimental Dry Eye Disease

2021 ◽  
Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Karoline Anne Orloff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Related Factor ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

scholarly journals Development of Lactoferrin-Loaded Liposomes for the Management of Dry Eye Disease and Ocular Inflammation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1698
Author(s):  
Ana López-Machado ◽  
Natalia Díaz-Garrido ◽  
Amanda Cano ◽  
Marta Espina ◽  
Josefa Badia ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ex Vivo ◽  
Visual Disturbance ◽  
Nasolacrimal Duct ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Lipid Film ◽  
Anti Inflammatory

Dry eye disease (DED) is a high prevalent multifactorial disease characterized by a lack of homeostasis of the tear film which causes ocular surface inflammation, soreness, and visual disturbance. Conventional ophthalmic treatments present limitations such as low bioavailability and side effects. Lactoferrin (LF) constitutes a promising therapeutic tool, but its poor aqueous stability and high nasolacrimal duct drainage hinder its potential efficacy. In this study, we incorporate lactoferrin into hyaluronic acid coated liposomes by the lipid film method, followed by high pressure homogenization. Pharmacokinetic and pharmacodynamic profiles were evaluated in vitro and ex vivo. Cytotoxicity and ocular tolerance were assayed both in vitro and in vivo using New Zealand rabbits, as well as dry eye and anti-inflammatory treatments. LF loaded liposomes showed an average size of 90 nm, monomodal population, positive surface charge and a high molecular weight protein encapsulation of 53%. Biopharmaceutical behaviour was enhanced by the nanocarrier, and any cytotoxic effect was studied in human corneal epithelial cells. Developed liposomes revealed the ability to reverse dry eye symptoms and possess anti-inflammatory efficacy, without inducing ocular irritation. Hence, lactoferrin loaded liposomes could offer an innovative nanotechnological tool as suitable approach in the treatment of DED.

Sign in / Sign up

Export Citation Format

Share Document