RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis.

Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie
Yalong DangNils A Loewen

Abstract

This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. 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. 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 T...Continue Reading

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Citations

Mar 29, 2019·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Chao WangNils A Loewen
Aug 28, 2020·Current Eye Research·Tomokazu FujimotoToshihiro Inoue
Mar 8, 2019·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Nuno Moura-CoelhoRita Pinto Proença
May 7, 2020·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Si ChenNils A Loewen

Related Concepts

RKI-1447
Metazoa
Glaucoma, Open-Angle
Physiologic Intraocular Pressure
Phagocytosis
Family suidae
Thiazoles
Trabecular Meshwork Structure
Carmol
Ocular Hypotension

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