Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye

Daull, Philippe; Feraille, Laurence; Barabino, Stefano; Cimbolini, Nicolas; Antonelli, Sophie; Mauro, Virgine; Garrigue, Jean-Sébastien

doi:10.1016/j.exer.2016.10.016

Cited by 28 publications

(36 citation statements)

References 32 publications

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“…39,61 As mentioned above, various anti-inflammatory drugs, such as topical steroids and cyclosporine, have been widely used to treat DED, and studies have shown that anti-inflammatory treatment has a beneficial effect on tear secretion, tear film stability, and ocular surface integrity. 62,63 In addition, as oxidative stress has a potent role in the pathogenesis of DED, antioxidative treatment has shown therapeutic effects against DED, proven by the improvement in various ocular surface parameters. 61 Therefore, we further investigated the effects of CJ extract on various clinical parameters, including tear volume, tear film BUT, and corneal fluorescein staining in a mouse model of EDE.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Lee

Choi

Cui

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee HS, Choi J-H, Cui L, et al. Anti-inflammatory and antioxidative effects of Camellia japonica on human corneal epithelial cells and experimental dry eye: in vivo and in vitro study. Invest Ophthalmol Vis Sci. 2017;58:119658: -120758: . DOI:10.1167 PURPOSE. To analyze the anti-inflammatory and antioxidative effects of Camellia japonica (CJ) on human corneal epithelial (HCE) cells and its therapeutic effects in a mouse model of experimental dry eye (EDE). METHODS.Camellia japonica extracts of varying concentrations (0.001%, 0.01%, and 0.1%) were used to treat HCE cells. Dichlorofluorescein diacetate (DCF-DA) and dihydroethidium (DHE) assays were performed. The production of peroxiredoxin (PRX) 1-6 and manganesedependent superoxide dismutase (MnSOD) in HCE cells was assessed using Western blot analysis. Furthermore, eye drops containing 0.001%, 0.01%, or 0.1% CJ extract or a balanced salt solution (BSS) were applied to the EDE. Clinical parameters were measured 7 days after treatment. The levels of inflammatory markers and intracellular reactive oxygen species (ROS) were measured.RESULTS. Treatment with 0.01% and 0.1% CJ extracts decreased apoptosis in HCE cells. In addition, band intensities of PRX 1, 4, and 5, as well as MnSOD, after hydrogen peroxide (H 2 O 2 ) treatment showed a significant improvement after pretreatment with 0.01% and 0.1% CJ extracts. Mice treated with 0.1% CJ extract showed significantly improved clinical parameters when compared to those of the EDE control and BSS groups. A significant decrease in the levels of inflammatory markers and intracellular ROS was observed in the 0.01% and 0.1% CJ extract groups.CONCLUSIONS. Camellia japonica extracts promoted antioxidative protein expression and suppressed apoptosis in HCE cells. Furthermore, CJ extracts improved clinical signs of dry eye and reduced oxidative stress and the expression of inflammatory markers, suggesting that eye drops containing CJ extract could be used as an adjunctive treatment for dry eye.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Lee

Choi

Cui

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Daull et al [2016] introduced cationic emulsion of cyclosporine A (0.1%) for the treatment of dry eye in the mouse model. It is also reported that cationic emulsion of cyclosporine A is very efficient in the management of corneal epithelium lesion [Daull et al, 2016]. It is also reported that cationic emulsion of cyclosporine A is very efficient in the management of corneal epithelium lesion [Daull et al, 2016].…”

Section: Management Of Delayed Ocular Complications Medical Managementsmentioning

confidence: 99%

“…Results of another study showed that cyclosporine ophthalmic drop two times daily decreased lymphatic cell counts and increased goblet cell counts in bulbar conjunctiva in cytological conjunctival smear in mustard gas exposed patients [Panahi et al, 2014d]. Daull et al [2016] introduced cationic emulsion of cyclosporine A (0.1%) for the treatment of dry eye in the mouse model. They stated that this new formulation is more effective than 1% methylprednisolone in the management of dry eye.…”

Section: Medical Managementsmentioning

confidence: 99%

“…They stated that this new formulation is more effective than 1% methylprednisolone in the management of dry eye. It is also reported that cationic emulsion of cyclosporine A is very efficient in the management of corneal epithelium lesion [Daull et al, 2016]. Tacrolimus has been described as an effective drug in the treatment of keratoconjunctivitis, controlling the inflammation in ocular tissues, and improving the tear film stability [Moscovici et al, 2015;Chatterjee and Agrawal, 2016].…”

Section: Medical Managementsmentioning

confidence: 99%

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Ocular Effects of Sulfur Mustard and Therapeutic Approaches

Panahi

Rajaee

Sahebkar

2017

J of Cellular Biochemistry

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Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes, and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis, and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication, and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD), and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation, and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin, and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. J. Cell. Biochem. 118: 3549-3560, 2017. © 2017 Wiley Periodicals, Inc.

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“…6,7,18 Nonsteroid antiinflammatory compounds are therefore preferred for the long-term treatment of DED patients, and CsA has demonstrated positive results in an animal model of DED and in clinical trials. [8][9][10][19][20][21] Various CsA ophthalmic preparations are currently available for use: 0.05% CsA anionic emulsion (Restasis®, Allergan, Irvine, CA, USA), 0.1% CsA cationic emulsion (Ikervis®, Santen, Evry, France), and hospital compound preparations of CsA (at concentrations up to 2% CsA). 22 CsA exerts its anti-inflammatory action via its binding to cyclophilin A and the subsequent inhibition of calcineurin.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Daull

Barabino

Feraille³

et al. 2019

Current Eye Research

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Purpose/Aim: Inflammation is recognized as playing an etiological role in dry eye disease. This study aimed to assess the efficacy of various topical cyclosporine A (CsA) formulations on cornea inflammatory markers in a mouse model of dry eye. Material and Methods: Six-to 7-week-old mice treated with scopolamine were housed in a controlled environment room to induce dry eye. Following dry eye confirmation by corneal fluorescein staining (CFS), the mice were treated three times a day with: 0.05%CsA (Restasis, Allergan), 0.1%CsA (Ikervis, Santen), 1%CsA oil solution, and 0.5% loteprednol etabonate (LE, Lotemax, Baush+Lomb), or left untreated. Aqueous tear production and CFS scores were assessed during the treatment period, and corneas were collected to measure the expression profile of a selection of inflammatory genes. Results: After 7 days of treatment, the CFS scores were reduced by 21%, 31%, and 44% with 0.05%CsA, 0.1%CsA, and 1%CsA eye drops, respectively. By contrast, 0.5% LE did not decrease corneal fluorescein staining at day 10. A statistically significant dose-dependent CFS reduction was observed only between the 0.05% and 1%CsA formulations. The gene expression profiles indicated that 12, 18, 17 genes were downregulated by 0.05%CsA, 0.1%CsA, 1%CsA, respectively. Among them, the genes significantly downregulated were: IL1A, IL1R1, and TLR4 with 0.05%CsA; H2-Eb1, IL1A, IL1B, IL1RN, IL6, TGFB2, TGFB3, TLR2, TLR3, and TLR4 with 0.1%CsA; IL1B, IL6, TGFB3, and TLR4 with 1%CsA. TGFB1 and TGFBR1 were the only genes upregulated in all groups, but only TGFB1 upregulation reached significance. IL6RA was significantly upregulated by 0.05%CsA. Conclusions: This study indicates that the three CsA formulations effectively modulated TLR4, TGFβ1, IL1, and IL6 pathways to reduce corneal epithelium lesions in a mouse model of severe dry eye. The study also suggests that the different anti-inflammatory eye drops modulated inflammatory genes in a slightly different manner. ARTICLE HISTORY

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Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye

Cited by 28 publications

References 32 publications

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Ocular Effects of Sulfur Mustard and Therapeutic Approaches

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

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