The purpose of the study was to determine the quantitative characteristics of IGF-1 binding sites in lens cells and to investigate its ability to modulate cell growth, in particular by inducing integrin expression. Studies were carried out in bovine lens epithelial cells in culture. IGF-1 receptor binding parameters were measured from saturation experiments with 125I-IGF-1. Scatchard plot indicates one class of high affinity sites (Kd = 2.5 +/- 1.5 nM). In addition, we showed that this growth factor was synthesized and released by lens cells. The characteristics of the receptor sites are in accordance with the effects of the growth factor (e.g. stimulation of DNA synthesis) in the range of nM concentrations. Moreover, by incubating cells with IGF-1 (12 nM) for 40 hr we demonstrated that the expression of integrin, the fibronectin receptor, was activated (N = 885 +/- 169 x 10(3) sites/cell vs N = 453 +/- 105 x 10(3) sites/cell in control cultures) without modification of its affinity (Kd congruent to 16 x 10(-8) M). These new data emphasize the role of IGF-1 in the regulation of migration, proliferation and differentiation of mature lens cells.
Opacification of the posterior lens capsule, (secondary cataract) , is one of the major complications of extracapsular cataract extraction. The lens epithelial cells remaining after surgery migrate and proliferate along posterior capsule, and give rise to structures such as pearls and cells with contractile properties, which considerably hamper vision. One pharmacological approach aimed at limiting this phenomenon would be to stop this cell migration, thus inhibiting their proliferation. It has been shown that cells adhere and migrate on their support via adhesion molecules such as integrins. Generally, the tripeptide sequence ArgGly-Asp (RGD) is the recognition motif for these receptors. In this study, cell adhesion inhibition in the presence of RGD peptides and derivatives was measured on extracellular matrix and lens capsule. One of these compounds, the [Na-acetyl-NG(H+) -arginyl]-glycyl-[Cß(H)-Ca-benzyl]-aspartamid-HCl] (LCM 1910), significantly inhibited cell migration at millimolar concentrations, and could be of interest in prevention of secondary cataract.
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