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O. Geyer, O. Genina, M. Pines; Collagen Synthesis by Conjunctival Fibroblasts in Culture: Response to Halofuginone . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1206.
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Purpose: Collagen deposition is largely responsible for scar formation, an undesirable outcome of glaucoma filtering surgery. Because halofuginone was found to inhibit collagen type I gene expression and collagen synthesis in animal models characterized by excessive deposition of collagen, we examined its effect on collagen synthesis from fibroblasts cultured from human conjunctiva. Methods: Human Tenon's capsule fibroblasts were obtained at the time of cataract surgery and established in individual cell cultures. Cell proliferation was measured by cell counting techniques after dissociation with trypsin/EDTA. Cell cultures were also incubated with radio-labeled proline and collagen synthesis was evaluated by digestion with collagenase. In addition, RNA isolation and Northern blot analysis were used to determine collagen alpha 1(I) gene expression. Results: Halofuginone caused a dose-dependent inhibition in fibroblast cell proliferation. Collagen dependent protein synthesis was inhibited by halofuginone with a dose-dependency. A halofuginone-induced decrease in collagen gene expression was found and it exhibited a halofuginone dose-dependent inhibition. Conclusions: Halofuginone is a novel and promising new modality to prevent collagen synthesis and scarring in glaucoma patients going through surgery.
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