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RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis.
Dang, Yalong; Wang, Chao; Shah, Priyal; Waxman, Susannah; Loewen, Ralitsa T; Loewen, Nils A.
Afiliación
  • Dang Y; Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Suite 819, Pittsburgh, PA, 15213, USA.
  • Wang C; Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Suite 819, Pittsburgh, PA, 15213, USA.
  • Shah P; Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
  • Waxman S; Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Suite 819, Pittsburgh, PA, 15213, USA.
  • Loewen RT; Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, Newark, NJ, USA.
  • Loewen NA; Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Suite 819, Pittsburgh, PA, 15213, USA.
Graefes Arch Clin Exp Ophthalmol ; 257(1): 101-109, 2019 Jan.
Article en En | MEDLINE | ID: mdl-30456419
PURPOSE: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. METHODS: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/ml for 48 h before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. RESULT: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 h. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 h (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. CONCLUSION: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Malla Trabecular / Urea / Hipotensión Ocular / Fibras de Estrés / Quinasas Asociadas a rho / Presión Intraocular Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiazoles / Malla Trabecular / Urea / Hipotensión Ocular / Fibras de Estrés / Quinasas Asociadas a rho / Presión Intraocular Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania