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The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts.
Futakuchi, Akiko; Inoue, Toshihiro; Fujimoto, Tomokazu; Inoue-Mochita, Miyuki; Kawai, Motofumi; Tanihara, Hidenobu.
Afiliación
  • Futakuchi A; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Inoue T; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: noel@da2.so-net.ne.jp.
  • Fujimoto T; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Inoue-Mochita M; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Kawai M; Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
  • Tanihara H; Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Exp Eye Res ; 149: 107-115, 2016 08.
Article en En | MEDLINE | ID: mdl-27394186
The most common cause of glaucoma surgery failure is scar formation induced by activation of wound-healing responses and resultant fibrosis at the surgical site. We investigated the effects of ripasudil, a Rho kinase inhibitor, on activation of human conjunctival fibroblasts (HConF). HConF were pretreated with different concentrations of ripasudil for 1 h before addition of transforming growth factor (TGF)-ß2, followed by incubation for 48 h. TGF-ß2-treated fibroblasts exhibited a significant increase in expression of α-smooth muscle actin (α-SMA), a marker of fibroblast-to-myofibroblast differentiation, and this increase was significantly suppressed, in a dose-dependent manner, by pretreatment with ripasudil. Ripasudil pretreatment also significantly attenuated TGF-ß2-induced fibronectin production and collagen gel contraction. TGF-ß2 increased both the number of viable cells and the number of cells in the G2/M phase of the cell cycle; these effects were attenuated by pretreatment with ripasudil. In addition, we explored the effects of ripasudil on stimulation of HConF by activated macrophages. Human monocytic cell line THP-1 cells were differentiated into M1 or M2 macrophage-like cells, and HConF were treated with conditioned media derived from these macrophages in the presence or absence of ripasudil. Conditioned medium from M2 macrophage-like cells induced a significant increase in α-SMA expression, viable cell numbers, and gel contraction, all of which were significantly suppressed by ripasudil. Thus, overall, ripasudil attenuated activation of human conjunctival fibroblasts. Ripasudil may be of therapeutic utility, preventing excessive scarring after glaucoma filtration surgery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfonamidas / Glaucoma / Cicatriz / Conjuntiva / Isoquinolinas Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfonamidas / Glaucoma / Cicatriz / Conjuntiva / Isoquinolinas Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido