EXPRESSION OF FOS FAMILY AND JUN FAMILY PROTOONCOGENES DURING CORNEALEPITHELIAL WOUND-HEALING

Purpose. While transformation of epithelial cells to a motile form is the first step in wound healing of the corneal epithelium, the migrato ry mechanism in these cells is not fully understood. We studied the ex pression of proto-oncogene mRNAs: c-fos; c-jun; fos B; jun B; jun D in injured corneal epithelium using in situ hybridization. Moreover, we examined immunolocalization of c-Fos and c-Jun protein products to elu cidate the transcriptional activation prior to the onset of migration in corneal epithelium. Methods. An epithelial defect was made on one c ornea of 60 Wistar rats. The affected eye was enucleated immediately ( within 5 min) or was allowed to bed for 15, 30, 60, 90, 120 and 180 mi n. Frozen sections were processed for in situ hybridization with c-fos , c-jun, fos B, jun B and jun D mRNAs or were stained with anti-c-fos and anti-c-jun antibodies. Results. Fifteen min after the epithelial a blation, weak signals for c-fos and c-jun mRNAs were detected in the c orneal epithelium surrounding the wound. These signals reached a peak 30 to 60 min after ablation, but were no longer evident at 120 min. Im munoreactivities for these proteins were also detected in the same are a at 60 to 120 min after the epithelial ablation. Fos B mRNA was detec ted in the same region at 30 min after the ablation, and reached its p eak after 30 to 60 min, but was no longer evident at 120 min. Jun B mR NA was detected in the epithelium around the defect 60 min after the a blation, later than the other proto-oncogenes, and reached its peak af ter 90 min. The message for jun D was detected in normal epithelium, a nd was not affected by wounding. Conclusions. These findings indicate that transcriptional activation of epithelial cells is initiated in th e early phase after epithelial ablation, before the cells start to mig rate, and that these proto-oncogene products may play important roles in wound healing in corneal epithelium. The time lag of the peak of ex pression of these proto-oncogenes might suggest the different roles fo r each proto-oncogene in this process.