IN VITRO TOXICITY OF BENZALKONIUM CHLORIDE (BAC) TO OCULAR SURFACE CELLS AND PRESERVATIVE-INDUCED DRY EYE.

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.

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NaCl-induced hyperosmotic stress as an in vitro dry eye model potentiated by synergic toxic effects of Benzalkonium chloride on conjunctival epithelial cells

Toxicology Letters ◽

10.1016/j.toxlet.2011.05.546 ◽

2011 ◽

Vol 205 ◽

pp. S155 ◽

Cited By ~ 1

Author(s):

C. Clouzeau ◽

D. Godefroy ◽

L. Riancho ◽

W. Rostene ◽

C. Baudouin ◽

...

Keyword(s):

Epithelial Cells ◽

Dry Eye ◽

Benzalkonium Chloride ◽

Hyperosmotic Stress ◽

Toxic Effects ◽

Eye Model ◽

Conjunctival Epithelial Cells

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Comparative Study of In Vitro Ocular Surface Cytotoxicity of a Fixed Combination of 0.5% Timolol/1% Dorzolamide Eyedrop and Its Components with 0.005% Benzalkonium Chloride

Biocontrol Science ◽

10.4265/bio.17.115 ◽

2012 ◽

Vol 17 (3) ◽

pp. 115-120 ◽

Cited By ~ 2

Author(s):

MASAHIKO AYAKI ◽

ATSUO IWASAWA ◽

YOSHIMI NIWANO

Keyword(s):

Comparative Study ◽

Ocular Surface ◽

Benzalkonium Chloride ◽

Fixed Combination

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The Protective Effect of Polygonum cuspidatum (PCE) Aqueous Extract in a Dry Eye Model

Nutrients ◽

10.3390/nu10101550 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1550 ◽

Cited By ~ 7

Author(s):

Bongkyun Park ◽

Ik Lee ◽

Soo-Wang Hyun ◽

Kyuhyung Jo ◽

Tae Lee ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Aqueous Extract ◽

Dry Eye ◽

Lacrimal Gland ◽

Ocular Surface ◽

Corneal Epithelial Cell ◽

Heme Oxygenase 1 ◽

Polygonum Cuspidatum

Dry eyes are caused by highly increased osmolarity of tear film, inflammation, and apoptosis of the ocular surface. In this study, we investigated the effect of Polygonum cuspidatum (PCE) aqueous extract in in vivo and in vitro dry eye models. Dry eye was induced by excision of the lacrimal gland and hyperosmotic media. In vivo, oral administration of PCE in exorbital lacrimal gland-excised rats recovered tear volume and Mucin4 (MUC4) expression by inhibiting corneal irregularity and expression of inflammatory cytokines. In vitro, hyperosmotic media induced human corneal epithelial cell (HCEC) cytotoxicity though increased inflammation, apoptosis, and oxidative stress. PCE treatment significantly inhibited expression of cyclooxygenase-2 and inflammatory cytokines (interleukin-6 and tumor necrosis factor-α), and activation of NF-κB p65 in hyperosmolar stress-induced HCECs. Hyperosmolarity-induced increase in Bcl-2-associated X protein (BAX) expression and activation of cleaved poly (ADP-ribose) polymerase and caspase 3 were attenuated in a concentration-dependent manner by PCE. PCE treatment restored anti-oxidative proteins such as heme oxygenase-1 (HO-1), superoxide dismutase-1 (SOD-1), and glutathione peroxidase (GPx) in hyperosmolar stress-induced HCECs. These data demonstrate that PCE prevents adverse changes in the ocular surface and tear fluid through inhibition of hyperosmolar stress-induced inflammation, apoptosis, and oxidation, suggesting that PCE may have the potential to preserve eye health.

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Evidence of Polyphenols Efficacy against Dry Eye Disease

Antioxidants ◽

10.3390/antiox10020190 ◽

2021 ◽

Vol 10 (2) ◽

pp. 190

Author(s):

Gaia Favero ◽

Enrico Moretti ◽

Kristína Krajčíková ◽

Vladimíra Tomečková ◽

Rita Rezzani

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Tear Film ◽

Dry Eye Disease ◽

Eye Disease ◽

Beneficial Effects ◽

Underlying Causes ◽

Ophthalmic Drug

Dry eye disease is a multifactorial pathology compromising the quality of life of patients, resulting in significant damage of the ocular surface and discomfort. The current therapeutical strategies are not able to definitively resolve the underlying causes and stop the symptoms. Polyphenols are promising natural molecules that are receiving increasing attention for their activity/effects in counteracting the main pathologic mechanisms of dry eye disease and reducing its symptoms. In the present review, a deep literature search focusing on the main polyphenols tested against dry eye disease was conducted, analyzing related in vitro, in vivo, and clinical studies to provide a comprehensive and current review on the state of the art. Polyphenols present multiple effects against dry eye diseases-related ocular surface injury. In particular, the observed beneficial effects of polyphenols on corneal cells are the reduction of the pathological processes of inflammation, oxidative stress, and apoptosis and modulation of the tear film. Due to numerous studies reporting that polyphenols are effective and safe for treating the pathological mechanisms of this ocular surface disease, we believe that future studies should confirm and extend the evidence of polyphenols efficacy in clinical practice against dry eye disease and help to develop new ophthalmic drug(s).

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