3-Adrenergic Receptors Regulate Retinal Endothelial Cell Migration and Proliferation*

Sympathetic nerves may play a role in vascular disorders of the eye. In the present study, we hypothesized that activation of 3-adrenergic receptors on retinal endothelial cells would promote migration and proliferation of these cells, two markers of an angiogenic phenotype. We show, for the first time, expression of 3adrenergic receptors on cultured retinal endothelial cells. Activation of these receptors with BRL37344, a specific 3-adrenergic receptor agonist, promoted migration that was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K), the mitogen activated protein kinase component MEK, and matrix metalloproteinases (MMPs) 2 and 9. BRL37344 stimulated proliferation, which could be blocked by inhibitors of Src, PI3K, and MEK. These cells also express the 1-adrenergic receptor with no 2-adrenergic receptor expression observed. Stimulation of the 1-adrenergic receptor with xamoterol, a specific partial agonist, did not promote proliferation or migration. These results support the hypothesis that 3-adrenergic receptors play a role in proliferation and migration of cultured human retinal endothelial cells.