Innate Immunity Laboratory, Institute of Experimental Medicine (CONICET/National Academy of Medicine of Buenos Aires), Buenos Aires, Argentina.
Medical Affairs, Poen Laboratories, Buenos Aires, Argentina.
Transl Vis Sci Technol. 2024 Oct 1;13(10):31. doi: 10.1167/tvst.13.10.31.
The purpose of this study was to investigate the effect of sodium hyaluronate (SH) on benzalkonium chloride (BAK)-induced toxicity in the ocular surface epithelium and corneal nerves.
Ocular surface epithelial cells from Balb/c mice were cultured with 0.1% to 0.4% SH and 0.001% to 0.01% BAK and their metabolic activity, viability, and wound repair capacity were assessed in vitro. Following a controlled corneal wound, re-epithelialization and recovery of epithelial barrier function and mechanosensitivity were measured in Balb/c mice treated with 0.4% SH 3 times/day and 0.01% BAK twice daily for 3 weeks. Nerve morphology was assessed by confocal microscopy of corneal whole mounts.
Whereas BAK exposure reduced metabolic activity, viability, and wound repair ability of ocular epithelial cells in vitro, pretreatment with SH ameliorated BAK toxicity in a concentration-dependent manner. The highest SH concentration partially reversed the effects of 0.01% BAK in vitro and increased the corneal healing rate of BAK-exposed mice. Although all corneal wounds closed after 4 days, continuous SH treatment improved corneal barrier dysfunction 18 days after wounding and accelerated the recovery of corneal mechanical sensitivity to baseline levels in BAK-exposed mice. SH treatment also increased corneal nerve density in the wounded area after 3 weeks.
SH mitigates BAK-associated ocular epithelial and neurotoxicity in a concentration-dependent manner.
Commercially available, high-concentration SH formulations may have added benefits in treating BAK-associated ocular surface toxicity.
本研究旨在探讨透明质酸钠（SH）对苯扎氯铵（BAK）诱导的眼表上皮细胞和角膜神经毒性的影响。
体外培养 Balb/c 小鼠眼表上皮细胞，用 0.1%至 0.4% SH 和 0.001%至 0.01% BAK 处理，评估其代谢活性、活力和伤口修复能力。在对 Balb/c 小鼠进行控制的角膜创伤后，用 0.4% SH 每天 3 次和 0.01% BAK 每天 2 次处理 3 周，测量再上皮化和上皮屏障功能及机械敏感性的恢复情况。通过角膜整体 mounts 的共聚焦显微镜评估神经形态。
BAK 暴露降低了体外眼表上皮细胞的代谢活性、活力和伤口修复能力，而 SH 预处理以浓度依赖的方式减轻了 BAK 的毒性。最高 SH 浓度部分逆转了 0.01% BAK 的体外作用，并增加了 BAK 暴露小鼠的角膜愈合率。尽管所有角膜伤口在 4 天后闭合，但连续的 SH 治疗改善了受伤后 18 天的角膜屏障功能障碍，并加速了 BAK 暴露小鼠角膜机械敏感性恢复到基线水平。SH 治疗还增加了 3 周后受伤区域的角膜神经密度。
SH 以浓度依赖的方式减轻 BAK 相关的眼表上皮和神经毒性。
医脉通
