We investigated the protective effects of
mannitol on
corneal damage caused by
benzalkonium chloride (BAC), which is used as a preservative in commercially available
timolol maleate eye drops, using rat debrided corneal epithelium and a human cornea epithelial cell line (
HCE-T). Corneal
wounds were monitored using a fundus camera TRC-50X equipped with a digital camera;
eye drops were instilled into rat eyes five times a day after corneal epithelial abrasion. The viability of
HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the
eye drops were determined using rabbits. The corneal wound healing rate and rate constant (kH), as well as cell viability, were higher following treatment with 0.005% BAC
solution containing 0.5%
mannitol than in the case BAC
solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without
mannitol. In addition, the kH for rat eyes instilled with commercially available
timolol maleate eye drops containing 0.5%
mannitol was significantly higher than that for eyes instilled with
timolol maleate eye drops without
mannitol, and the addition of
mannitol did not affect the corneal penetration or IOP reducing effect of the
timolol maleate eye drops. A preservative system comprising BAC and
mannitol may provide effective
therapy for
glaucoma patients requiring long-term treatment with
anti-glaucoma agents.