May 1991
Volume 32, Issue 6
Free
Articles  |   May 1991
Inhibition of growth factor effects in retinal pigment epithelial cells.
Author Affiliations
  • K H Leschey
    Department of Ophthalmology, University of Virginia Health Sciences Center, Charlottesville.
  • J Hines
    Department of Ophthalmology, University of Virginia Health Sciences Center, Charlottesville.
  • J H Singer
    Department of Ophthalmology, University of Virginia Health Sciences Center, Charlottesville.
  • S F Hackett
    Department of Ophthalmology, University of Virginia Health Sciences Center, Charlottesville.
  • P A Campochiaro
    Department of Ophthalmology, University of Virginia Health Sciences Center, Charlottesville.
Investigative Ophthalmology & Visual Science May 1991, Vol.32, 1770-1778. doi:
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    • Get Citation

      K H Leschey, J Hines, J H Singer, S F Hackett, P A Campochiaro; Inhibition of growth factor effects in retinal pigment epithelial cells.. Invest. Ophthalmol. Vis. Sci. 1991;32(6):1770-1778.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Several agents were examined for their effect on growth factor-stimulated processes in retinal pigment epithelial (RPE) cells. DNA synthesis was assessed by 3H-thymidine incorporation in density-arrested cells using previously determined maximally effective concentrations of various growth factors with and without test substances. Cell migration was assessed in Boyden chamber assays. For each test substance, trypan blue exclusion was used to determine noncytotoxic concentrations, and the effect of several concentrations were assessed on selected growth factors. The most effective, nontoxic concentration was then used for comparisons. Two cationic proteins, protamine and histone type II B, caused inhibition of RPE chemotaxis and 3H-thymidine incorporation induced by several growth factors, but a cationic polypeptide, polylysine, did not. Protamine and histone, were particularly effective inhibitors of acidic and basic fibroblast growth factors (FGF) but not if they were exposed to cells and then removed before growth factor addition. They had no effect on serum-stimulated chemotaxis or 3H-thymidine incorporation even when used in the presence of serum. Three anionic substances, heparin, pentosan polysulfate, and suramin, also inhibited RPE chemotaxis and 3H-thymidine incorporation induced by several different growth factors. They were less effective inhibitors of the FGFs than protamine and histone but were better inhibitors of serum-induced effects. Also unlike protamine and histone, the anionic substances maintained their inhibitory effect even when removed before growth factor addition. Since migration and proliferation of RPE cells are important processes in the pathogenesis of proliferative vitreoretinopathy, these agents and their mechanism of action deserve further study for potential therapeutic applications.

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