Topical hyaluronan alone promotes corneal epithelial cell migration whereas combination with benzalkonium chloride impairs epithelial wound healing

Abstract

Purpose: To evaluate the effects of topical hyaluronan (HA) on corneal epithelial wound healing when administered with or without benzalkonium chloride (BAC).

Methods: A cultured human corneal epithelial cell line (HCE-T) was subjected to in vitro scratch assays and in situ epithelial migration was evaluated in organ-cultured rabbit corneas. The corneal epithelium of C57BL/6J mice was also evaluated to determine in vivo wound healing. An in vivo imaging system was also used to evaluate the effects of HA on eye drop retention on the ocular surface.

Results: The findings revealed the promotion of HCE-T migration, in situ rabbit corneal epithelial migration, and in vivo wound healing in mouse corneal epithelium by HA. Pre-treatment with HA also protected against delayed epithelial wound healing in BAC in vitro. However, pre-treatment with 3 mg/mL HA did not show a protective effect against BAC in vivo, but instead delayed epithelial wound healing and increased detection of cleaved caspase-3. This suggested that HA promotes the retention of BAC on the ocular surface. The instilled HA was retained after 15 min, at a significantly higher rate than for phosphate-buffered saline.

Conclusions: The combination of HA and BAC impaired wound healing in the corneal epithelium.

Keywords:

• Hyaluronan
• benzalkonium chloride
• corneal epithelial wound healing
• eye drops

Acknowledgements

The use of HCE-T was kindly permitted by Kaoru Araki-Sasaki, MD, PhD, in Hoshiagoka Medical Centre, Japan Community Health care Organisation. Scientific writing assistance was provided by Editage.

Disclosure statement

Satoshi Seino, Ryosuke Matsuoka, Yasunobu Masuda, and Masaaki Kunou are employed at Kewpie Corp, which funded this research.

Data availability statement

The data that support the findings of this study are available from the corresponding author, SS, upon reasonable request.

Additional information

Funding

This work was supported by Kewpie Corp. and the Laboratory Animal Centre Wakayama Medical University.