Role of CD18 and CD31 in Corneal Wound Healing and Neutrophil Migration

Abstract

Abstract: : Purpose: In response to corneal injury, neutrophils (PMNs) migrate into the corneal stroma. We examined the role of leukocyte CD18 integrins and PECAM–1 (CD31), in corneal wound repair and PMN migration within the corneal stroma. Methods: C57BL/6 wild type mice and mice deficient in CD18 or CD31 were anesthetized with Nembutal. Corneal epithelial wounds (2 mm diameter) were made through the whole epithelium with a trephine. Injured corneas were excised at 6h intervals and PMN infiltration was quantified by deconvolution microscopy. Transmission electron microscopy (TEM) was used to evaluate PMN interactions with corneal keratocytes. Results: Re–epithelialization in wild type mice occurred within 18–24h, but was significantly delayed by 6–12h in both CD18 –/– and CD31–/– deficient mice. This correlated with a delay in the peak PMN influx into the central cornea. In CD18 –/– mice, PMN extravasation was delayed by 24h, but subsequent migration through the corneal stroma was rapid. Conversely, the onset of PMN extravasation was normal in CD31 –/– mice, but PMN migration through the corneal stroma was impaired. TEM revealed that PMN migration within the corneal stroma involved extensive surface contacts with keratocytes. Morphometric analysis showed that CD18 was not required for PMN close contacts with keratocytes, whereas CD31–deficient PMNs showed a marked reduction in close keratocyte contacts (p<0.05). Conclusions: Absence of CD18 or CD31 delays corneal re–epithelialization. CD31, but not CD18, is required for efficient PMN migration within the corneal stroma. PMN migration appears to involve extensive surface contacts with keratocytes, a process regulated in part by CD31.

Keywords: cornea: stroma and keratocytes • inflammation • wound healing