Effects of Benzalkonium Chloride Upon the Corneal Epithelium Studied With Scanning Electron Microscopy

Journal of Ocular Pharmacology and Therapeutics

Kumagami

Shimoda

et al. 2011

Methods: Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by two Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC.Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives EDTA, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay.Results: Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of for BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC.

Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Polyoxyethylene Hydrogenated Castor Oil Modulates Benzalkonium Chloride Toxicity: Comparison of Acute Corneal Barrier Dysfunction Induced by Travoprost Z and Travoprost

Journal of Ocular Pharmacology and Therapeutics

Kumagami

Shimoda

et al. 2011

“…Some of these adjuvants act as ocular penetrating enhancers promoting drug penetration through the strong corneal barrier and modifying the physiochemical property of drugs (Saettone et al, 1996: Sasaki et al, 1999. At the same time, however, they destroy the corneal epithelial structure, especially the transcellular integration of superficial cells, which is mainly maintained by tight junctions (Burstein, 1980: Tonjum, 1975. Therefore, investigation of the effect on the cornea by ophthalmic drugs and adjuvants is important.…”

Section: Discussionmentioning

confidence: 99%

A novel in vivo corneal trans-epithelial electrical resistance measurement device

Journal of Pharmacological and Toxicological Methods

Mohamed

Onizuka

et al. 2015

Purpose: To develop a device that is capable of easily measuring corneal transepithelial electrical resistance (TER) and changes in the corneal barrier function. Methods:We had previously developed an in vivo method for measuring corneal TER using intraocular electrode. This method can be used to precisely measure the decline of the corneal barrier function after instillation of benzalkonium chloride (BAC). In order to lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. TER was then calculated by subtracting the electrical resistance, which lacked the corneal epithelial input, from the whole electrical resistance that was measured between the electrodes. Slit lamp examination and scanning electron microscopy (SEM) were used to determine safety of the new device. Corneal TER changes after exposure to 0.02% BAC were determined using the new device as well as SEM and transmission electron microscopy (TEM).Results: Slit lamp examination before and after exposure of rabbits' corneas to the sensor confirmed safety of the device. SEM examination revealed no difference of the corneal epithelium which exposed to the new device with normal corneas. SEM and 3 TEM pictures revealed damaged microvilli and tight junctions after instillation of 0.02% BAC. TER change after treatment with 0.02%BAC was similar to those determined by the established anterior chamber method. Conclusion:We succeeded to develop a less invasive device for corneal TER measurement in vivo in animals. This new device may be applicable in the future for clinical use in humans.

“…1 In ophthalmology, commonly administered pharmacotherapeutic agents contain commercially produced BAC, which consists of 3 homologs that have different N-alkyl chain lengths (C12, C14, and C16). On the other hand, numerous studies have revealed that there are deleterious corneal effects associated with BAC that include destabilization of the tear film, 2 death of corneal and conjunctival epithelial cells, [3][4][5][6] morphological changes in the corneal epithelial cells, [7][8][9][10][11] and the reduction of the corneal epithelial barrier function. [12][13][14] It has been reported in previous studies that the carbon chain lengths of phosphatidylcholines or nonionic surfactants can influence the degree of hemolysis of red blood cells.…”

mentioning

confidence: 99%

Influence of Alkyl Chain Length of Benzalkonium Chloride on Acute Corneal Epithelial Toxicity

Kumagami

Shimoda

et al. 2010

Cornea

Purpose: To evaluate acute corneal epithelial toxicity induced by benzalkonium chloride (BAC) homologs with different alkyl chain lengths using an in vivo electrophysiological method.Methods: BAC homologs with C12, C14, and C16 alkyl chain lengths were used at concentrations of 0.0025%, 0.005%, and 0.01%, respectively. Cytotoxicity of BAC homologs on the normal rabbit corneal epithelial cells was examined by using a WST-1 assay. Corneal transepithelial electrical resistance (TER) was measured in living Japanese white rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. TER changes were then evaluated after a 60-second exposure to these BAC homologs. Morphological changes in corneal epithelium after exposure to the BAC homologs were examined using scanning electron microscopy. The antimicrobial activity of BAC homologs against Escherichia coli was also assessed.Results: All BAC homologs caused cytotoxicity and corneal barrier dysfunction in a concentration-dependent manner. However, the degree of corneal toxicity differed among the BAC homologs. Based on cytotoxicity and TER measurement, C14-BAC caused the greatest corneal impairment followed in order of severity by mixed BAC/C16-BAC and C12-BAC. Scanning electron microscopy images indicated an intact corneal epithelium after exposure to 0.005% C12-BAC, whereas 0.005% C14-BAC damaged the epithelium. There were no remarkable differences noted in the antimicrobial activity among the BAC homologs.Conclusions: Acute corneal epithelial toxicity induced by BAC homologs depends on the alkyl chain length. Thus, the use of C12-BAC instead of commercially available BAC is potentially safer for patients undergoing ophthalmological pharmacotherapy.