Effects of benzalkonium chloride and cyclosporine applied topically to rabbit
            conjunctiva: a histomorphometric study

Faria, Nubia Vanessa Lima de; Sampaio, Manuella; Viapiana, Gabriela N.; Seabra, Nathália Mendonça de; Russ, Heloisa Helena Abil; Montiani‐Ferreira, Fabiano; Mello, Paulo Augusto de Arruda

doi:10.5935/0004-2749.20190062

Cited by 4 publications

(6 citation statements)

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“…In the original rabbit dry eye model, Xiong et al [15] found a lower corneal staining score after the instillation of 0.1% BAC for 2 weeks compared to the current study, but a higher loss of goblet cells. As expected, other authors found similar ocular surface damage [23][24][25][26][27][28][29][30][31][32][33]. Additionally, some of them reported a reduction in epithelial corneal thickness [24,29,30], which is another marker that could be evaluated in this animal model.…”

Section: Discussionsupporting

confidence: 80%

“…is rabbit dry eye model has been used to measure the efficacy of different eye drops and drug delivery systems for dry eye treatment [23][24][25][26][27][28][29][30][31][32]. Some studies applied their treatments while the BAC was being instilled [23,[27][28][29]31] and other studies after the instillation of BAC, during the period of reversibility of the dry eye model [24-26, 30, 32]. Li et al [43] studied the stability of the original model of Xiong et al [15], establishing that the signs of dry eye were sustained between 2 and 3 weeks after the last instillation of 0.1% BAC.…”

Section: Discussionmentioning

confidence: 99%

“…Animal models based on the topical administration of BAC allow the evaluation of different dry eye markers related to tear quality, ocular surface damage, and inflammation. In rabbits, several studies used this model to evaluate the efficacy of different eye drops containing hyaluronic acid [23,24], povidone [23], epigallocatechin gallate [24,25], virally inactivated serum [26], carboxymethyl pullulan [27], or cyclosporine A [28]. is model was also used to evaluate new treatments using drug delivery systems such as nanoparticles modified with anti-inflammatories [29] or epigallocatechin gallate/hyaluronic acid [30] and cyclosporine A-eluting contact lenses [31].…”

Section: Introductionmentioning

confidence: 99%

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Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

Carpena-Torres

Pintor

Lara

et al. 2020

Journal of Ophthalmology

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Purpose. To optimize a rabbit dry eye model induced by topical instillation of benzalkonium chloride (BAC), reduce the days of instillation of the original model by increasing the concentration of BAC from 0.1% to 0.2%. Materials and Methods. An experimental, prospective, and randomized study was performed on 10 male New Zealand white rabbits, divided into two groups, considering both eyes: 5 rabbits as control (n = 10) and 5 rabbits with 0.2% BAC treatment (n = 10). Saline solution (control) and 0.2% BAC were instilled for 5 consecutive days, twice daily. Tear secretion with and without anesthesia, tear breakup time, tear osmolarity, corneal staining, conjunctival hyperemia, density of goblet cells, height of mucin cloud, and transcript levels of IL-6 were measured before and after the treatment. Results. After the instillation of 0.2% BAC for 5 consecutive days, there was a significant increase in tear secretion without anesthesia P<0.001, corneal staining P<0.001, conjunctival hyperemia P<0.001, and levels of IL-6 mRNA P=0.005 compared to the control group. Conversely, there was a decrease in tear secretion with anesthesia P<0.001, tear breakup time P=0.007, tear osmolarity P<0.001, density of goblet cells P<0.001, and height of mucin cloud P<0.001. Conclusions. The topical instillation of 0.2% BAC for 5 consecutive days, twice daily, was a proper procedure to induce a rabbit dry eye model, reducing the number of days of instillation compared to the original model (14 days).

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

Carpena-Torres

Pintor

Lara

et al. 2020

Journal of Ophthalmology

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“…Low doses of BAK can induced proapoptotic efect on conjutival cells lines involving, as shown in vitro, reactive oxygen species and, therefore, oxidative stress reducing the number of goblet cells [19]. This cytotoxicity was proportional to the BAK concentration.…”

Section: Bak Toxicity In Globet Cellsmentioning

confidence: 74%

Glaucoma and Dry Eye

Baez¹,

Iturria²

2022

Dry Eye Syndrome - Modern Diagnostic Techniques and Advanced Treatments

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Glaucoma treatment is closely related to the appearance or worsening of dry eye symptoms. The current topical treatment produces chronic inflammation that affects globet cells, meibomian glands and cornea, which translates into a decrease in the quantity and quality of the tear. It is characterized by increased osmolarity, which perpetuates damage to the ocular surface. Preservatives currently play a fundamental role in damage the ocular surface. There are numerous studies that have shown their toxic effects on the eye. Currently there are numerous preservative-free formulations and new therapies that allow us to improve the condition of the ocular surface in patients with glaucoma. A rational treatment is proposed using the different approaches available in the literature.

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“…In addition, according to a previous clinical report, the goblet cell density was significantly greater than that of the baseline in the inferior bulbar conjunctiva after a 6-week treatment of cyclosporine emulsion [ 41 ], however, this treatment effect, like those reported elsewhere, was not observed in our study using the BAC induction model. The difference might result from the relatively short-term exposure to an agent with a higher preservative concentration than that found in commercially available eye drops [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model

et al. 2021

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Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompatibility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis®, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Importantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical application. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E2 (PGE2) in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES.

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Effects of benzalkonium chloride and cyclosporine applied topically to rabbit conjunctiva: a histomorphometric study

Cited by 4 publications

References 0 publications

Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

Glaucoma and Dry Eye

Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model

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