Early Wound Healing Response to Epithelial Scrape Injury in the Human Cornea

Abstract

Abstract: : Purpose: To examine the early wound healing response to epithelial scrape in a unique model involving the human corneas. During the last decade, our knowledge of corneal wound healing has increased tremendously. Most of the information came from animal studies. The current study was designed to validate knowledge obtained from previous animal studies in human patients. Methods: Patients with choroidal melanoma or orbital malignancy with a normal cornea, scheduled for enucleation or exenteration were asked to participate. This study was approved by the Institutional Review Board of the University of Washington. Corneal epithelial scrape was performed at different time points prior to enucleation. The corneal-scleral button was removed and cryopreserved in OCT medium. Corneas were examined for apoptosis using the TUNEL assay and for mitosis using Ki67 immunocytochemistry. Results: Three corneas were studied: 4 hours, 60 hours and control (no epithelial scrape). Keratocyte apoptosis was detected by the TUNEL assay in keratocytes in the anterior stroma in scraped corneas (4 hours was less than 60 hours), but was not detected in the control cornea (Figure 1). There was no Ki67 binding in keratocytes in the stroma in the 4 hour wounded or control tissue. There was Ki67 binding in a few keratocytes in the stroma in the wound area subjacent to the area devoid of keratocytes in 60 hour wounded tissue. Conclusion: Results obtained in human corneas were very similar to those in animal models, including rabbits and mice. Keratocyte apoptosis occurs in the anterior stroma of human corneas after epithelial scrape injury. This incites a proliferative response in the subjacent stoma that starts during the first 2 days after injury. Keratocyte apoptosis is a good target to control or modulate the wound healing response following corneal surgery.  

Keywords: 370 cornea: basic science • 323 apoptosis/cell death • 374 cornea: stroma and keratocytes