Annexin A2 promotes proliferative vitreoretinopathy in response to a macrophage inflammatory signal in mice

Abstract

Proliferative vitreoretinopathy is a vision-threatening response to penetrating ocular injury, for which there is no satisfactory treatment. In this disorder, retinal pigment epithelial cells, abandon their attachment to Bruch’s membrane on the scleral side of the retina, transform into motile fibroblast-like cells, and migrate through the retinal wound to the vitreal surface of the retina, where they secrete membrane-forming proteins. Annexin A2 is a calcium-regulated protein that, in complex with S100A10, assembles plasmin-forming proteins at cell surfaces. Here, we show that, in proliferative vitreoretinopathy, recruitment of macrophages and directed migration of retinal pigment epithelial cells are annexin A2-dependent, and stimulated by macrophage inflammatory protein-1α/β. These factors induce translocation of annexin A2 to the cell surface, thus enabling retinal pigment epithelial cell migration following injury; our studies reveal further that treatment of mice with intraocular antibody to either annexin A2 or macrophage inflammatory protein dampens the development of proliferative vitreoretinopathy in mice.