Effects of Commercial 4th Generation Fluoroquinolones on Corneal Epithelial Barrier Function in Experimental Murine Dry Eye

Abstract

Abstract: : Purpose: To compare the effects of topically applied 4^th generation fluoroquinolone antibiotics (gatifloxacin and moxifloxacin) on corneal epithelial barrier function in experimental dry eye. Methods: Dry eye was created in C57BL6 mice by subcutaneous injection of 0.25mg scopolamine 4 times daily and exposure to an air draft and low humidity environment for up to 5 days. Both eyes of each mouse were treated with 1 µl of either 0.3% gatifloxacin (Zymar) or 0.5% moxifloxacin (Vigamox) 4 times daily. Corneal epithelial permeability to 0.5% sodium fluorescein was measured in 6 untreated eyes and 6 eyes treated with each antibiotic with a Fluorotron master^TM. Expression of the tight junction associated protein ZO–1 in the corneal epithelium was evaluated by scanning laser confocal microscopy. Results: Corneal epithelial permeability to fluorescein showed a slight, but non significant increase at day 2 with return to baseline by day 5 in the gatifloxacin treated eyes. Eyes treated with moxifloxacin showed a significant and progressive increase in corneal fluorescein permeability at days 2 and 5. Permeability was significantly greater in moxifloxacin treated eyes than in gatifloxacin treated eyes at day 5. A normal honeycomb pattern of ZO–1 immunoreactivity was noted in gatifloxacin treated eyes on days 2 and 5. In contrast, moxifloxacin treated eyes showed focal loss of membrane associated ZO–1 staining at days 2 and 5. Conclusions: Commercial moxifloxacin caused a greater disruption of corneal epithelial barrier function than gatifloxacin. This may be due in part to toxic effects on epithelial tight junctions.

Keywords: antibiotics/antifungals/antiparasitics • cornea: epithelium • cornea: tears/tear film/dry eye