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S. Mukherjee, C. Guidry; The Influence of the Insulin-Like Growth Factor System on Retinal Pigment Epithelial Cell Tractional Force Generation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5720.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the influence of the insulin-like growth factor system on retinal pigment epithelial cell (RPE) tractional force generation as a potential contributing mechanism in the pathogenesis of proliferative vitreoretinopathy (PVR).
Insulin-like growth factor system ligands (IGF-I and IGF-II), insulin-like growth factor binding protein (IGFBP), and non-IGFBP binding analogue (R3IGF-I ) effects were evaluated in tissue culture assays involving incubation of cells on three-dimensional collagen gels with subsequent monitoring of changes in gel thickness.
RPE generate tractional forces in response to IGF-I and, to a lesser extent, IGF-II. Increased RPE responsiveness to R3IGF-I reflected modest endogenous binding protein production. IGFBP effects on RPE tractional force generation were inhibitory overall and generally dependent upon growth factor binding. IGFBP-2, -3 and -5 were effective inhibitors of both IGF-I and IGF-II while IGFBP-6 reduced cell responses to IGF-II only. IGFBP direct effects on the cells were binding protein-specific and comparatively modest. IGFBP-1 had detectable stimulatory effects whereas IGFBPs -3, -4, -5 and -6 inhibited RPE responses to R3IGF-I.
IGF-I and -II are potent promoters of RPE tractional force generation in vitro with IGF-I being the more effective stimulus. RPE produce modest, but nonetheless detectable amount of functional IGFBPs. The effects of the six high-affinity IGFBPs on RPE responses are generally inhibitory and primarily mediated through growth factor binding. While the role of IGFBPs in PVR pathobiology is unknown, our observations indicate that these proteins can regulate RPE responses to IGF and may constitute a previously unrecognized vitreous regulatory system of RPE activity in PVR.
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