Abstract
Purpose :
Recent evidence shows that epithelial stem/progenitor cells in barrier tissues such as the skin, airways and intestines retain a memory of previous injuries, which enables tissues to accelerate barrier restoration after subsequent injuries. The corneal epithelium, the outermost layer of the cornea, is a frontline barrier for the eye and maintained by epithelial stem/progenitor cells in the limbus. Herein, we provided the evidence that inflammatory memory also exists in the cornea.
Methods :
To address whether an injury to the corneal epithelium exerts a lasting influence on the cornea following subsequent injury, we made an abrasion injury to the cornea in 8-week-old BALB/c mice by scraping off the central 2-mm-diameter corneal epithelium (day 0). At day 28, we re-challenged the injury-recovered cornea with the same abrasion injury or with different chemical/mechanical assaults (application of ethanol to the corneal surface and removal of its epithelium). The eyes were daily observed, and at day 35, the corneas were extracted for molecular assays.
To evaluate the beneficial effects of transient inflammatory stimulus on the healing ability of corneal epithelium in a clinical setting, we examined a cohort of patients with ocular Sjögren's syndrome (SjS) and identified 11 patients who had experienced infectious keratitis over the disease course. Then, we sequentially reviewed medical records and evaluated corneal PEEs in an individual patient before and after infection.
Results :
In mice, eyes that had been exposed to corneal epithelial injury exhibited faster re-epithelialization of the cornea and lower levels of inflammatory cytokines following subsequent injury (either the same or different type of injury), compared to naïve eyes without previous injury. In ocular Sjögren’s syndrome patients, corneal punctate epithelial erosions were significantly reduced after experiencing infectious injury, compared to before infection.
Conclusions :
These data demonstrate that previous exposure of the corneal epithelium to inflammatory stimuli enhances corneal wound healing in response to a secondary assault, pointing to the presence of non-specific inflammatory memory in the cornea.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.