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Corneal endothelial repair. Regulation of prostaglandin E2 synthesis
1Department of Ophthalmology and Visual Sciences, University of Louisville, School of Medicine, Kentucky 40202, USA.
Purpose:
The authors have investigated the hypothesis that prostaglandin E2 (PGE2) synthesis is regulated during corneal endothelial wound healing. Previous studies have shown that PGE2 is an important mediator of endothelial mitosis, migration, and differentiation.
Methods:
Biosynthesis of PGE2 was investigated in a wound closure model of the cultured rabbit corneal endothelium and in cultures treated with experimental agents. Prostaglandin E2 synthesis was measured by enzyme-linked immunosorbent assay. Pharmacologic experiments were designed to evaluate the contributions of protein kinases, phospholipase A2, and cyclooxygenase to endogenous PGE2 synthesis.
Results:
Prostaglandin E2 synthesis is increased markedly in response to injury and is proportional to the extent of wounding. Biosynthesis of PGE2 returns to basal levels concurrently with recovery of the injury. Synthesis is dependent on the activities of protein kinase C (PKC), phospholipase A (PLA), and cyclooxygenase. Two forms of cyclooxygenase are present in corneal endothelial cells, and pharmacologic studies indicate that the activity of the COX 2 contributes to injury-dependent PGE2 synthesis.
Conclusions:
Prostaglandin E2 synthesis is increased in injured corneal endothelial cells. This synthesis is dependent on the coordinated regulation of PKC, PLA, and cyclooxygenase. Prostaglandin E2 synthesis presents an attractive target for pharmacologic manipulation of endothelial recovery from injury.