Glucocorticoids Suppress Corneal Lymphangiogenesis

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Purpose:To determine whether glucocorticoids suppress corneal lymphatic vessel growth (lymphangiogenesis) or induce lymphatic vessel regression.Methods:We measured human lymphatic endothelial cell proliferation and collagen-induced tubulogenesis in culture conditions with and without dexamethasone, a potent glucocorticoid. We developed a modification of the mouse corneal suture model that allowed us to visualize lymphatic vessel growth (with suture) or regression (suture removed) using immunofluorescence and microscopic techniques. We administered dexamethasone or vehicle control to mice with sutured corneas. We visualized and quantified the corneal lymphatic vessels. We measured vascular endothelial growth factor-C and tumor necrosis factor-α messenger RNA expression in unsutured or sutured corneas using quantitative reverse transcriptase–polymerase chain reaction.Results:High-dose dexamethasone did not change the proliferation or tubulogenesis properties of human lymphatic endothelial cells in vitro. We demonstrated suppressed corneal lymphatic vessel growth rather than lymphatic vessel regression in mice treated with dexamethasone. Expressions of corneal vascular endothelial growth factor-C and tumor necrosis factor-α messenger RNA were similar in mice treated with or without dexamethasone.Conclusions:Dexamethasone suppressed new lymphatic vessel growth and did not induce lymphatic vessel regression. These findings identify a novel mechanism of glucocorticoid action: suppression of corneal lymphangiogenesis.

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