Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity.

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

SH mitigates BAK-associated ocular epithelial and neurotoxicity in a concentration-dependent manner.

TRANSLATIONAL RELEVANCE

Commercially available, high-concentration SH formulations may have added benefits in treating BAK-associated ocular surface toxicity.