Purchase this article with an account.
C Guidry, R McKinney, JL King; Insulin-like Growth Factor Binding Protein Regulation of Müller Cell-generated Tractional Forces . Invest. Ophthalmol. Vis. Sci. 2002;43(13):667.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previous studies demonstrated that vitreous insulin-like growth factor-I (IGF-I) activity is increased in proliferative retinal diseases and that this same growth factor stimulates tractional force generation by Müller cells. Members of the insulin-like growth factor binding protein family (IGFBPs) are also present in normal vitreous, but the normal complement is altered in proliferative retinal disease. IGFBPs are known to modulate IGF-I biological activity, though the specific effects of each IGFBP can vary with the experimental system. With respect to tractional force generation and Müller cells, the effects of IGFBPs on vitreous IGF-I activity are unknown. As disease-related changes in vitreous IGFBPs may contribute to net changes in IGF-I activity, our purpose was to characterize IGFBP-specific effects on IGF-I-induced Müller cells and determine the biosynthetic potential of Müller cells as a source of IGFBPs. Methods: Tractional force generation was examined using a tissue culture model in which IGF-I stimulated porcine Müller cell contraction of collagen gels. Recombinant IGFBPs 1 through 6 were tested for the ability to attenuate or enhance IGF-I-induced activity in dose-response assays of varying designs. Müller cell biosynthetic potential was examined using RT-PCR with IGFBP species-specific primers Results: IGF-I activity was variably attenuated by IGFBPs. IGFBP-3 inhibited IGF-I activity in a dose-dependent fashion with complete inhibition at a binding protein: growth factor molar ratio of 10:1. IGFBPs 2 and 4 were modestly inhibitory in the same range, IGFBPs 1 and 5 slightly inhibitory, and IGFBP-6 without effect. In the absence of IGF-I, IGFBPs lacked direct effects except for slightly enhanced matrix contraction by cells exposed to IGFBP-1. RT-PCR studies revealed potential expression of IGFBPs 3, 4, and 6 in normal retina, pre-contractile and contractile Müller cell phenotypes. IGFBP-4 product was weak but detectable in pre-contractile Müller cells while IGFBP-2 and IGFBP-4 products were prominent in contractile Müller cells. Conclusion: IGFBPs known to be present in normal vitreous can attenuate IGF-I-mediated tractional force generation by Müller cells. This suggests that IGFBP changes may contribute to net increases in IGF-I biological activity in disease. At present, IGFBP-3 is of particular interest. Paradoxically, Müller cells, a target of the growth factor activity, also have the capacity to produce IGF-I-attenuating IGFBPs.
This PDF is available to Subscribers Only