Vitreous-induced Modulation of Integrins in Retinal Pigment Epithelial Cells: Effects of Fibroblast Growth Factor-2

Abstract

Growth in the presence of vitreous results in transformation of human RPE cells from an epithelioid to a fibroblast-like appearance and leads to an elevation of the expression of α5 and α2 integrins, while the level of α3 integrin is reduced. These changes are inhibited by the presence of FGF-2. Vitreous treatment increases mobility, as does antibody neutralization of FGF-2 or antibody blockade of FGF receptors. The vitreous-induced rise in mobility depends on an increase in α5 integrin expression since it is inhibited by anti-α5 integrin antibodies. Expression of α5 integrin as a result of infection of RPE cells with an α5 integrin-encoding adenovirus induced morphological transformation and an increase in mobility similar to that seen with vitreous. It is concluded that a decrease in FGF-2 plays an important role in vitreous-induced alterations of RPE cell morphology, integrin expression and mobility. High FGF-2 levels prevent at least some of the increased mobility of RPE cells induced by vitreous. This is mediated via extracellular FGF-2 binding to FGF receptor(s) since antibodies to FGF-2 or to its receptor(s) mimic the effects of vitreous. Changes in mobility and morphology involve altered α5 integrin expression since mobility is blocked by antibodies against these proteins while elevated α5 integrin expression increases mobility and leads to morphological changes.