Evaluation of corneal toxicity of prostaglandin (PG) analogs using primary epithelial cell toxicity assay

Abstract

We have developed and reported a highly sensitive and simple toxicity assay system (primary epithelial cell toxicity assay) to detect the toxicity on corneal epithelium by measuring the area of epithelial cells regularly spreading from freshly cultured porcine corneal tissue. To evaluate the usefulness of this assay system in commercially available eye drops, the following four types of prostaglandin (PG) analogs were investigated: 0.005% latanoprost ophthalmic solution containing 0.02% benzalkonium chloride (BAK), 0.03% bimatoprost ophthalmic solution containing 0.005% BAK, 0.0015% tafluprost ophthalmic solution containing 0.001% BAK, and 0.004% travoprost ophthalmic solution without BAK. The outgrowth rates were 70.6 ± 23.0% for 0.004% travoprost ophthalmic solution, 59.3 ± 7.5% for 0.0015% tafluprost ophthalmic solution, 44.0 ± 7.6% for 0.03% bimatoprost ophthalmic solution, and 27.5 ± 10.0% for 0.005% latanoprost ophthalmic solution. Compared to the control, the outgrowth rates of all PG analogs were significantly decreased. The results suggest that the primary epithelial cell toxicity assay is a highly sensitive assay for detecting corneal epithelial toxicity of PG analogs. Therefore, this assay may be applied to the detection of corneal epithelial toxicity of other commercially available eye drops.