Investigative ophthalmology & visual science · 2018
Topical Ripasudil Suppresses Retinal Ganglion Cell Death in a Mouse Model of Normal Tension Glaucoma.
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Akaiwa Kei, Namekata Kazuhiko, Azuchi Yuriko, Sano Hiroki, Guo Xiaoli, Kimura Atsuko, Harada Chikako, Mitamura Yoshinori, Harada Takayuki
Аннотация
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.
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.
Предметные рубрики MeSH
Administration, OphthalmicAnimalsCell DeathDisease Models, AnimalElectroretinographyExcitatory Amino Acid Transporter 3ImmunoblottingImmunohistochemistryIntraocular PressureIsoquinolinesLow Tension GlaucomaMiceMice, Inbred C57BLMice, KnockoutPhosphorylationRetinal DegenerationRetinal Ganglion CellsSulfonamidesTomography, Optical CoherenceTonometry, Ocularp38 Mitogen-Activated Protein Kinasesrho-Associated Kinases