Changes in Corneal Epithelial Barrier Function and Zonula Occludens-1 Distribution with Concomitant Use of Silver Nitrate and Latanoprost in Rabbits

Purpose: This study investigated the effects of silver nitrate (AgNO 3 ), a preservative in ophthalmic solution, alone and in combination with latanoprost (LP), on corneal epithelial barrier function and zonula occludens-1 (ZO-1) distribution in the corneal epithelium of rabbits. Methods: Twelve adult male albino New Zealand white rabbits (weighing 3.0–3.5 kg) were the subjects in this study. These mature rabbits received five instillations at 5-min intervals of AgNO 3 (0.01, 0.1, or 1%), benzalkonium chloride (BAK 0.02%), LP (0.005%) alone, or LP combined with AgNO 3 (0.01 or 1%). Corneal resistance (CR) was measured, and histological analyses were performed. Results: AgNO 3 1% increased CR (108.2%); however, CR significantly decreased when combined with LP ( P < 0.05). Marked CR reduction was observed in the eyes administered BAK and LP + AgNO 3 1%. Immunostaining showed preserved ZO-1 in the eyes that received AgNO 3 1% and LP + AgNO 3 0.01%, whereas those that received BAK, LP alone, and LP + AgNO 3 1% demonstrated disrupted ZO-1. Conclusions: A high concentration of AgNO 3 with LP exacerbated corneal epithelial barrier impairment, which highlights the importance of preservative concentration control in ophthalmic formulations.