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ID 115192
Title Alternative
Ripasudil Promotes Neuroprotection
Author
Akaiwa, Kei Tokyo Metropolitan Institute of Medical Science|Tokushima University
Namekata, Kazuhiko Tokyo Metropolitan Institute of Medical Science
Azuchi, Yuriko Tokyo Metropolitan Institute of Medical Science
Sano, Hiroki Tokyo Metropolitan Institute of Medical Science|Tokushima University
Guo, Xiaoli Tokyo Metropolitan Institute of Medical Science
Kimura, Atsuko Tokyo Metropolitan Institute of Medical Science
Harada, Chikako Tokyo Metropolitan Institute of Medical Science
Harada, Takayuki Tokyo Metropolitan Institute of Medical Science|Tokushima University
Keywords
ripasudil
glaucoma
neuroprotection
intraocular pressure
p38
Content Type
Journal Article
Description
PURPOSE. To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma.
METHODS. Topical administration (5 μL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, the measurement of intraocular pressure (IOP), and histopathology analyses were performed at 5, 8, and 12 weeks old. Retrograde labeling of retinal ganglion cells (RGCs), immunoblot, and immunohistochemical analyses of phosphorylated p38 mitogen-activated protein kinase (MAPK) in the retina were performed at 8 weeks old.
RESULTS. Topical ripasudil ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old. Ripasudil reduced IOP and strongly suppressed the phosphorylation of p38 MAPK that stimulates RGC death in EAAC1 KO mice.
CONCLUSIONS. These results suggest that, in addition to IOP reduction, ripasudil prevents glaucomatous retinal degeneration by neuroprotection, which is achieved by suppressing cell-death signaling pathways.
Journal Title
Investigative Ophthalmology & Visual Science
ISSN
15525783
Publisher
Silverchair|The Association for Research in Vision and Ophthalmology
Volume
59
Issue
5
Start Page
2080
End Page
2089
Published Date
2018-04
Rights
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License(https://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences