Purpose: Oxidative stress plays an important role in pathogenesis of glaucoma. The purpose of this study is to investigate the novel effect of antiglaucoma drugs on the expression of antioxidant peroxiredoxins of trabecular meshwork (TM) cells.
Methods: The expression of the peroxiredoxin family was investigated using immortalized TM cell lines. Cells were treated with antiglaucoma drugs and analyzed for the expression of peroxiredoxin, and cellular sensitivity to oxidative stress. Furthermore, the effect of antiglaucoma drugs on the molecular regulation of the expression of peroxiredoxin was examined using a reporter assay and siRNA strategy.
Results: Glaucomatous TM cells highly express peroxiredoxin 2 when compared with normal TM cells. Nipradilol and timolol, but not latanoprost, induce the expression of peroxiredoxin 2 through the activation of the Foxo3a transcription factor. TM cells showed reduced sensitivity to H(2)O(2) when cells were treated with either nipradilol or timolol, but not with latanoprost. In addition, both Foxo3a and PRDX2 expression were enhanced by drug-induced signal transduction through its receptor.
Conclusions: These results indicate that both nipradilol and timolol possess a novel mechanism of action and function as potent protective agents against oxidative stress.
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http://dx.doi.org/10.1167/iovs.08-3061 | DOI Listing |
Clin Exp Ophthalmol
October 2024
Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Background: To evaluate and compare the long-term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. 'Long-term' is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs).
Methods: This systematic review and model-based network meta-analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs.
J Ophthalmol
April 2017
Tokyo New Drug Research Laboratories, Kowa Co. Ltd., 2-17-43 Noguchicho, Higashimurayama, Tokyo 189-0022, Japan.
Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP) by increasing conventional outflow through the trabeculae to Schlemm's canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys.
View Article and Find Full Text PDFNeurochem Int
December 2012
Department of Molecular Neurobiology, Kanazawa University, Kanazawa, Japan.
Nipradilol (Nip), which has α1- and β-adrenoceptor antagonist and nitric oxide (NO)-donating properties, has clinically been used as an anti-glaucomatous agent in Japan. NO mediates cellular signaling pathways that regulate physiological functions. The major signaling mechanisms mediated by NO are cGMP-dependent signaling and protein S-nitrosylation-dependent signalings.
View Article and Find Full Text PDFActa Ophthalmol
August 2012
Kanto Central Hospital, Tokyo, Japan Yotsuya-Shirato Eye Clinic, Tokyo, Japan.
Purpose: To prospectively study prognostic factors for normal-tension glaucoma (NTG) under treatment with topical β-blocker.
Methods: One hundred and forty-six eyes of 146 patients with NTG with a mean untreated intraocular pressure (IOP) of 14 mmHg, mild to moderate visual field damage and mean spherical equivalent refraction of -3.5 (-8.
Nippon Ganka Gakkai Zasshi
March 2011
Department of Ophthalmology, The University of Tokyo Graduate School of Medicine, Japan.
Pathogenesis of open-angle glaucoma involves both pressure-dependent damaging factors and pressure-independent damaging factors. The high prevalence of open-angle glaucoma with normal pressure (normal-tension glaucoma) in Japan implies that treatment of pressure-independent damaging factors in Japanese open-angle glaucoma patients is of importance. In an attempt to investigate the roles of pressure-independent damaging factors in open-angle glaucoma, we carried out basic and clinical studies and obtained the following results.
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