Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial...

Area of Science:

• Ophthalmology
• Molecular Biology
• Wound Healing Research

Background:

• Persistent corneal epithelial (CE) defects (PED) are characterized by a failure in rapid re-epithelialization post-injury.
• The underlying genetic mechanisms governing CE re-epithelialization in PED remain incompletely understood.
• Identifying key genes and pathways is crucial for developing effective treatments for corneal wound healing.

Purpose of the Study:

• To elucidate the gene network driving corneal re-epithelialization in persistent corneal epithelial defects (PED).
• To compare gene expression profiles in PED patients' corneal tissue and in response to tear treatments.
• To investigate the roles of specific genes in CE homeostasis, inflammation, and cell-cell communication during healing.

Main Methods:

• Collected epithelial scrapes and tear samples from PED patients and healthy controls (PRK group).
• Utilized quantitative real-time PCR (qRT-PCR) to analyze the expression of key genes (e.g., KLF4, GPX4, IL6, TNFα, IL8, desmoglein, E-cadherin).
• Assessed KLF4 localization via immunofluorescence and matrix metalloproteinase (MMP) activity using zymography.

Main Results:

• Kruppel-like factor 4 (KLF4) was downregulated in PED tissues but upregulated in tear-treated cells.
• Cell-cell communication genes showed decreased expression in PED tissues but increased expression with tear treatment.
• Pro-inflammatory genes (IL6, TNFα, IL8) were significantly upregulated in both conditions, with increased MMP9 activity observed upon tear treatment.

Conclusions:

• Tears may induce an acute pro-inflammatory state contributing to PED pathology, while PED tissues reflect a chronic inflammatory stage.
• Interferons and pro-inflammatory pathways are implicated in PED pathogenesis.
• These findings suggest potential therapeutic targets for enhancing corneal epithelialization in PED.