Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice

作者：Lili Ran, Jing Feng, Xia Qi, Ting Liu, Benxiang Qi, Kai Jiang, Zhenzhen Zhang, Yang Yu, Qingjun Zhou, Lixin Xie · 发表于：Investigative Ophthalmology & Visual Science · 年份：2023 · DOI：10.1167/iovs.64.1.19 · 被引用次数：13 · 研究领域：Ion Channels and Receptors、Connexins and lens biology、Ocular Surface and Contact Lens

Purpose: To reveal the role of cold-sensing transient receptor potential melastatin 8 (TRPM8) channels in corneal epithelial wound healing. Methods: Cold sensitivity, tear production, corneal thickness, and corneal opacity assessments were used to evaluate the effect of Trpm8 knockout on the ocular surface. A corneal epithelial wounding model was generated by scraping the corneal epithelium once or multiple times using C57BL/6J (wild-type [WT]) and Trpm8-/- mice. The processes of corneal epithelial repair and corneal epitheliopathy were observed and recorded. Corneas were collected for sequencing, immunofluorescence staining, hematoxylin and eosin staining, and quantitative PCR. Results: The perception of coldness, basal tear secretion, and corneal thickness were decreased in young Trpm8-/- mice compared with those in WT mice, except for the corneal sensitivity. Corneal opacity and increased corneal thickness were observed in aged Trpm8-/- mice. TRPM8 deficiency promoted corneal epithelial wound closure, consistent with the observed increase in Ki67-positive epithelial cells, and the pharmacological activation of TRPM8 in WT mice delayed corneal re-epithelization. After subjecting mice to multiple injuries, squamous metaplasia emerged in Trpm8-/- corneas, as verified by cytokeratin-1 and small proline-rich protein 1B-positive staining. The IFN-β and IFN-γ signaling pathways were significantly activated in Trpm8-/- mice, which was confirmed based on the up-regulated expression...