Cytotoxicity of prostaglandin analog eye drops preserved with benzalkonium chloride in multiple corneoconjunctival cell lines

Masahiko Ayaki¹, Atsuo Iwasawa<sup>2

1</sup>Department of Ophthalmology, Saitama National Hospital, Wako, ²Department of Clinical Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan

Purpose: This study evaluated the cytotoxicity of five prostaglandin analog ophthalmic ­solutions on four ocular surface cell lines, ie, Chang (human conjunctiva), SIRC (rabbit cornea), RC-1 (rabbit cornea), and BCE C/D-1b (bovine cornea).

Methods: Cell viability was measured by neutral red and MTT assays in cells treated for 10, 30, or 60 minutes with various doses of prostaglandins (undiluted, and 2- and 10-fold dilutions). The number of cell lines with viability ≥50% in the presence of selected dilution of the drug (CVS₅₀) was used for comparison. In addition, 24 cell viability comparisons (four cell lines, two assays, and three exposure times) were made between latanoprost (Xalatan^®) and each other solution at each dose. A comparison between the newly introduced tafluprost (Tapros^®) with 0.01% benzalkonium chloride was also made.

Results: The order of cell viability determined by CVS₅₀ was Travatan Z^® (travoprost with the SofZia system)> Tapros ≥ Travatan^® (travoprost) = Xalatan > Rescula^® (unoproston). This was consistent with the results of direct comparisons between Xalatan and the other drugs. There was no clear difference in cell viability between Tapros and benzalkonium chloride.

Conclusions: Use of two assays, multiple cell lines, and various dilutions and exposure times provided a unique evaluation of cytotoxicity among ophthalmic solutions. CVS₅₀ was useful for comparison of the cell viability of the solutions.

Keywords: glaucoma, cornea, cell viability score