Endothelial Mesenchymal Transition: A Therapeutic Target in Retrocorneal Membrane

Abstract

A single layer of corneal endothelial cells covers the posterior surface of the Descemet membrane. Normally, corneal endothelial cells do not proliferate, suggesting that factors inhibit their undergoing mitosis. Fibroblastic transformation of corneal endothelial cells due to syphilitic interstitial keratitis or alkali burn may result in stromal opacification. Various growth factors such as fibroblast growth factor 2 and transforming growth factor β are involved in "endothelial-mesenchymal transition (EnMT)." Endothelial wound-healing assay experiments revealed that cell migration toward artificial wound defect was mediated by p38 and c-Jun N-terminal kinase. To understand whether Smad signal might have an important role in EnMT regulation, gene transfer of Smad7 was employed to block transforming growth factor β/Smad signal in rat corneal endothelium 3 days before alkali burning. EnMT during healing interval after alkali burn was markedly suppressed by Smad7 overexpression associated with upregulation of cell proliferation. Therefore, blocking Smad signal effectively suppresses injury-induced EnMT and fibrogenic reaction by corneal endothelium without impairing repair of wound defect. Strategies that block Smad may be useful for prevention and treatment of fibrogenic disorders in the corneal endothelium.